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Gharib A, Marquez C, Meseguer-Beltran M, Sanchez-Sarasua S, Sanchez-Perez AM. Abscisic acid, an evolutionary conserved hormone: Biosynthesis, therapeutic and diagnostic applications in mammals. Biochem Pharmacol 2024; 229:116521. [PMID: 39251140 DOI: 10.1016/j.bcp.2024.116521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 08/26/2024] [Accepted: 09/05/2024] [Indexed: 09/11/2024]
Abstract
Abscisic acid (ABA), a phytohormone traditionally recognized for its role in plant stress responses, has recently emerged as a significant player in mammalian defense mechanisms. Like plants, various mammalian cell types synthesize ABA in response to specific health challenges, although the precise pathways remain not fully elucidated. ABA is associated with the regulation of inflammation and insulin signaling, prompting extensive research into its potential as a therapeutic agent for various diseases. ABA exerts its effects through its receptors, particularly PPAR-γ and LANCL-2, which serve as signaling hubs regulating numerous pathways. Through these interactions, ABA profoundly impacts mammalian health, and new ABA targets continue to be identified. Numerous studies in animal models demonstrate ABA's benefit in managing conditions such as neurological and psychiatric disorders, cancer, and malaria infections, all of which involve significant inflammatory dysregulation. In this manuscript we review the studies covering ABA synthesis and release in cell cultures, the signaling pathways regulated by ABA, and how these impact health in preclinical models. Furthermore, we highlight recent research suggesting that measuring ABA levels in human body fluids could serve as a useful biomarker for pathological conditions, providing insights into disease progression and treatment efficacy. This comprehensive review outlines the current understanding of ABA in mammalian pathophysiology, identifying gaps in knowledge, particularly concerning ABA biosynthesis and metabolism in mammals. In addition, this study emphasizes the need for clinical trials to validate the effectiveness of ABA-based therapies and its reliability as a biomarker for various diseases.
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Affiliation(s)
- Amir Gharib
- Neurobiotecnologia Group, Institute of Advanced Materiales (INAM), Universitat Jaume I, Avda. de Vicent Sos Baynat, S/n, 12071 Castelló de La Plana, Spain; Department of Laboratory Sciences, Borujerd Branch, Islamic Azad University, Borujerd, Iran
| | - Carlee Marquez
- Neurobiotecnologia Group, Institute of Advanced Materiales (INAM), Universitat Jaume I, Avda. de Vicent Sos Baynat, S/n, 12071 Castelló de La Plana, Spain
| | - Maria Meseguer-Beltran
- Neurobiotecnologia Group, Institute of Advanced Materiales (INAM), Universitat Jaume I, Avda. de Vicent Sos Baynat, S/n, 12071 Castelló de La Plana, Spain
| | - Sandra Sanchez-Sarasua
- Neurobiotecnologia Group, Institute of Advanced Materiales (INAM), Universitat Jaume I, Avda. de Vicent Sos Baynat, S/n, 12071 Castelló de La Plana, Spain; CNRS UMR 5293, Institut Des Maladies Neurodégénératives, Centre Paul Broca-Nouvelle Aquitaine, University of Bordeaux, Bordeaux, France.
| | - Ana M Sanchez-Perez
- Neurobiotecnologia Group, Institute of Advanced Materiales (INAM), Universitat Jaume I, Avda. de Vicent Sos Baynat, S/n, 12071 Castelló de La Plana, Spain.
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Iranmanesh Z, Dehestani M, Esmaeili-Mahani S. Discovering novel targets of abscisic acid using computational approaches. Comput Biol Chem 2024; 112:108157. [PMID: 39047594 DOI: 10.1016/j.compbiolchem.2024.108157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/16/2024] [Accepted: 07/17/2024] [Indexed: 07/27/2024]
Abstract
Abscisic acid (ABA) is a crucial plant hormone that is naturally produced in various mammalian tissues and holds significant potential as a therapeutic molecule in humans. ABA is selected for this study due to its known roles in essential human metabolic processes, such as glucose homeostasis, immune responses, cardiovascular system, and inflammation regulation. Despite its known importance, the molecular mechanism underlying ABA's action remain largely unexplored. This study employed computational techniques to identify potential human ABA receptors. We screened 64 candidate molecules using online servers and performed molecular docking to assess binding affinity and interaction types with ABA. The stability and dynamics of the best complexes were investigated using molecular dynamics simulation over a 100 ns time period. Root mean square fluctuations (RMSF), root mean square deviation (RMSD), solvent-accessible surface area (SASA), radius of gyration (Rg), free energy landscape (FEL), and principal component analysis (PCA) were analyzed. Next, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method was employed to calculate the binding energies of the complexes based on the simulated data. Our study successfully pinpointed four key receptors responsible for ABA signaling (androgen receptor, glucocorticoid receptor, mineralocorticoid receptor, and retinoic acid receptor beta) that have a strong affinity for binding with ABA and remained structurally stable throughout the simulations. The simulations with Hydralazine as an unrelated ligand were conducted to validate the specificity of the identified receptors for ABA. The findings of this study can contribute to further experimental validation and a better understanding of how ABA functions in humans.
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Affiliation(s)
- Zahra Iranmanesh
- Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Maryam Dehestani
- Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.
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Han T, Xu Y, Liu H, Sun L, Cheng X, Shen Y, Wei J. Function and Mechanism of Abscisic Acid on Microglia-Induced Neuroinflammation in Parkinson's Disease. Int J Mol Sci 2024; 25:4920. [PMID: 38732130 PMCID: PMC11084589 DOI: 10.3390/ijms25094920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 04/27/2024] [Accepted: 04/28/2024] [Indexed: 05/13/2024] Open
Abstract
Parkinson's disease (PD), as a neurologically implemented disease with complex etiological factors, has a complex and variable pathogenesis. Accompanying further research, neuroinflammation has been found to be one of the possible factors in its pathogenesis. Microglia, as intrinsic immune cells in the brain, play an important role in maintaining microenvironmental homeostasis in the brain. However, over-activation of neurotoxic microglia in PD promotes neuroinflammation, which further increases dopaminergic (DA) neuronal damage and exacerbates the disease process. Therefore, targeting and regulating the functional state of microglia is expected to be a potential avenue for PD treatment. In addition, plant extracts have shown great potential in the treatment of neurodegenerative disorders due to their abundant resources, mild effects, and the presence of multiple active ingredients. However, it is worth noting that some natural products have certain toxic side effects, so it is necessary to pay attention to distinguish medicinal ingredients and usage and dosage when using to avoid aggravating the progression of diseases. In this review, the roles of microglia with different functional states in PD and the related pathways inducing microglia to transform into neuroprotective states are described. At the same time, it is discussed that abscisic acid (ABA) may regulate the polarization of microglia by targeting them, promote their transformation into neuroprotective state, reduce the neuroinflammatory response in PD, and provide a new idea for the treatment of PD and the selection of drugs.
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Affiliation(s)
- Tingting Han
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China; (T.H.); (Y.X.); (H.L.); (X.C.)
| | - Yuxiang Xu
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China; (T.H.); (Y.X.); (H.L.); (X.C.)
| | - Haixuan Liu
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China; (T.H.); (Y.X.); (H.L.); (X.C.)
| | - Lin Sun
- College of Chemistry and Molecular Sciences, Henan University, Kaifeng 475004, China
| | - Xiangshu Cheng
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China; (T.H.); (Y.X.); (H.L.); (X.C.)
| | - Ying Shen
- Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China;
| | - Jianshe Wei
- Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China; (T.H.); (Y.X.); (H.L.); (X.C.)
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Parajuli KR, Jung Y, Taichman RS. Abscisic acid signaling through LANCL2 and PPARγ induces activation of p38MAPK resulting in dormancy of prostate cancer metastatic cells. Oncol Rep 2024; 51:39. [PMID: 38624012 PMCID: PMC10804438 DOI: 10.3892/or.2024.8698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 12/12/2023] [Indexed: 04/17/2024] Open
Abstract
Prostate cancer (PCa) is one the most common malignancies in men. The high incidence of bone metastasis years after primary therapy suggests that disseminated tumor cells must become dormant, but maintain their ability to proliferate in the bone marrow. Abscisic acid (ABA) is a stress response molecule best known for its regulation of seed germination, stomal opening, root shoot growth and other stress responses in plants. ABA is also synthesized by mammalian cells and has been linked to human disease. The aim of the present study was to examine the role of ABA in regulating tumor dormancy via signaling through lanthionine synthetase C‑like protein 2 (LANCL2) and peroxisome proliferator activated receptor γ (PPARγ) receptors. ABA signaling in human PCa cell lines was studied using targeted gene knockdown (KD), western blotting, quantitative PCR, cell proliferation, migration, invasion and soft agar assays, as well as co‑culture assays with bone marrow stromal cells. The data demonstrated that ABA signaling increased the expression of p21, p27 and p16, while inhibiting viability, migration, invasion and colony size in a reversable manner without toxicity. ABA also induced p38MAPK activation and NR2F1 signaling. Targeted gene KD of LANCL2 and PPARγ abrogated the cellular responses to ABA. Taken together, these data demonstrate that ABA may induce dormancy in PCa cell lines through LANCL2 and PPARγ signaling, and suggest novel targets to manage metastatic PCa growth.
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Affiliation(s)
- Keshab Raj Parajuli
- Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL 35294, USA
| | - Younghun Jung
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
| | - Russell S. Taichman
- Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL 35294, USA
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA
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Wagner T, Bangoura B, Wiedmer S, Daugschies A, Dunay IR. Phytohormones regulate asexual Toxoplasma gondii replication. Parasitol Res 2023; 122:2835-2846. [PMID: 37725257 DOI: 10.1007/s00436-023-07968-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 09/04/2023] [Indexed: 09/21/2023]
Abstract
The protozoan Toxoplasma gondii (T. gondii) is a zoonotic disease agent causing systemic infection in warm-blooded intermediate hosts including humans. During the acute infection, the parasite infects host cells and multiplies intracellularly in the asexual tachyzoite stage. In this stage of the life cycle, invasion, multiplication, and egress are the most critical events in parasite replication. T. gondii features diverse cell organelles to support these processes, including the apicoplast, an endosymbiont-derived vestigial plastid originating from an alga ancestor. Previous studies have highlighted that phytohormones can modify the calcium-mediated secretion, e.g., of adhesins involved in parasite movement and cell invasion processes. The present study aimed to elucidate the influence of different plant hormones on the replication of asexual tachyzoites in a human foreskin fibroblast (HFF) host cell culture. T. gondii replication was measured by the determination of T. gondii DNA copies via qPCR. Three selected phytohormones, namely abscisic acid (ABA), gibberellic acid (GIBB), and kinetin (KIN) as representatives of different plant hormone groups were tested. Moreover, the influence of typical cell culture media components on the phytohormone effects was assessed. Our results indicate that ABA is able to induce a significant increase of T. gondii DNA copies in a typical supplemented cell culture medium when applied in concentrations of 20 ng/μl or 2 ng/μl, respectively. In contrast, depending on the culture medium composition, GIBB may potentially serve as T. gondii growth inhibitor and may be further investigated as a potential treatment for toxoplasmosis.
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Affiliation(s)
- Tina Wagner
- Institute of Inflammation and Neurodegeneration, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Berit Bangoura
- Department of Veterinary Sciences, Wyoming State Veterinary Laboratory, University of Wyoming, Laramie, WY, 82070, USA.
| | - Stefanie Wiedmer
- Faculty of Biology, Institute of Zoology, Technische Universität Dresden, Dresden, Germany
| | - Arwid Daugschies
- Institute of Parasitology, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany
| | - Ildiko Rita Dunay
- Institute of Inflammation and Neurodegeneration, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Subodh, Ravina, Priyanka, Narang J, Mohan H. Biosensors for phytohormone Abscisic acid and its role in humans: A review. SENSORS INTERNATIONAL 2023. [DOI: 10.1016/j.sintl.2023.100234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/24/2023] Open
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Wong A, Bi C, Chi W, Hu N, Gehring C. Amino acid motifs for the identification of novel protein interactants. Comput Struct Biotechnol J 2022; 21:326-334. [PMID: 36582434 PMCID: PMC9791077 DOI: 10.1016/j.csbj.2022.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/06/2022] [Accepted: 12/06/2022] [Indexed: 12/14/2022] Open
Abstract
Biological systems consist of multiple components of different physical and chemical properties that require complex and dynamic regulatory loops to function efficiently. The discovery of ever more novel interacting sites in complex proteins suggests that we are only beginning to understand how cellular and biological functions are integrated and tuned at the molecular and systems levels. Here we review recently discovered interacting sites which have been identified through rationally designed amino acid motifs diagnostic for specific molecular functions, including enzymatic activities and ligand-binding properties. We specifically discuss the nature of the latter using as examples, novel hormone recognition and gas sensing sites that occur in moonlighting protein complexes. Drawing evidence from the current literature, we discuss the potential implications at the cellular, tissue, and/or organismal levels of such non-catalytic interacting sites and provide several promising avenues for the expansion of amino acid motif searches to discover hitherto unknown protein interactants and interaction networks. We believe this knowledge will unearth unexpected functions in both new and well-characterized proteins, thus filling existing conceptual gaps or opening new avenues for applications either as drug targets or tools in pharmacology, cell biology and bio-catalysis. Beyond this, motif searches may also support the design of novel, effective and sustainable approaches to crop improvements and the development of new therapeutics.
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Affiliation(s)
- Aloysius Wong
- Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province 325060, China
- Wenzhou Municipal Key Lab for Applied Biomedical and Biopharmaceutical Informatics, Ouhai, Wenzhou, Zhejiang Province 325060, China
- Zhejiang Bioinformatics International Science and Technology Cooperation Center, Ouhai, Wenzhou, Zhejiang Province 325060, China
| | - Chuyun Bi
- Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province 325060, China
- Wenzhou Municipal Key Lab for Applied Biomedical and Biopharmaceutical Informatics, Ouhai, Wenzhou, Zhejiang Province 325060, China
- Zhejiang Bioinformatics International Science and Technology Cooperation Center, Ouhai, Wenzhou, Zhejiang Province 325060, China
| | - Wei Chi
- Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province 325060, China
| | - Ningxin Hu
- Department of Biology, College of Science and Technology, Wenzhou-Kean University, 88 Daxue Road, Ouhai, Wenzhou, Zhejiang Province 325060, China
| | - Chris Gehring
- Department of Chemistry, Biology & Biotechnology, University of Perugia, Perugia 06121, Italy
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Shabani M, Ranjbar H, Soti M, Naderi R. Central injection of abscisic acid attenuates mood disorders induced by subchronic stress in male mice. Brain Behav 2022; 12:e2796. [PMID: 36355391 PMCID: PMC9759152 DOI: 10.1002/brb3.2796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 09/10/2022] [Accepted: 10/08/2022] [Indexed: 11/12/2022] Open
Abstract
Stressful life increases the risk of mental and psychological disorders and cognitive deficits. Abscisic acid (ABA) is a plant hormone that has been recently discovered in mammalians. ABA is produced in response to stressful stimuli and it can reduce anxiety-like behaviors and depression and improve cognitive function. This study was designed to evaluate the effects of microinjection of ABA on depression, anxiety, passive avoidance learning and memory deficits induced by subchronic stress. ABA (10 and 15 μ $\umu $ g/mouse, i.c.v.) was administered one week after recovery period for 4 consecutive days. A three-session forced swimming test (FST) protocol for induction of subchronic stress was administered to the mice. Exploratory, anxiety-like behavior, depression and cognitive function were assessed 24 h after the last swim stress session. The results indicated that ABA (15 μ $\umu $ g/mouse) could ameliorate anxiety and depression induced by FST. In addition, ABA had no effect on the subchronic stress-induced cognitive impairments. Taken together, the results suggest that ABA could improve anxiety and depression induced by subchronic stress.
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Affiliation(s)
- Mohammad Shabani
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
| | - Hoda Ranjbar
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
| | - Monavareh Soti
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
| | - Reyhaneh Naderi
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
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Sereno AB, Dayane Pinto C, Antunes Andrade F, Aparecida Bertolazo da Silva M, Carvalho Garcia A, Carneiro Hecke Krüger C, José de Messias Reason I. Effects of okra (Abelmoschus esculentus (L.) Moench) on glycemic markers in animal models of diabetes: A systematic review. JOURNAL OF ETHNOPHARMACOLOGY 2022; 298:115544. [PMID: 35963420 DOI: 10.1016/j.jep.2022.115544] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 07/06/2022] [Accepted: 07/11/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Okra (Abelmoschus esculentus (L.) Moench) is traditionally used by different populations of Africa, América, Asia, and Europa to control diabetes. Although its action has been evaluated in several preclinical rodent trials, they have not been systematically analyzed. OBJECTIVE To evaluate the effectiveness of using okra in the treatment of diabetes in experimental rodent models. MATERIAL AND METHODS Controlled and randomized rodent animal trials with induced diabetes published between January 2000 and January 2021 were searched in the PubMed, Scopus, Scielo, and Web of Science databases. The search strategy included studies comprising the descriptors: animal species, diabetes induction method, intervention time, part of okra fruit used (whole, seeds, or peels), and dose as well as observed effects on biochemical and metabolic parameters. The systematic review was carried out according to the PRISMA statement, Cochrane bias risk tool (SYRCLE's RoB tool), and registered for systematic review protocols (PROSPERO). RESULTS A total of 326 articles were identified and after the exclusion of studies with gestational animal models, non-rodent animals, and non-diabetic animals, 11 studies involving 388 rodents were selected for the synthesis of results. The diabetes induction methods included streptozotocin, streptozotocin-nicotinamide, alloxan monohydrate, insulin resistance by high-fat diets or formulation described in AIN - 76, and feeding with high-fat food. Both Wistar albino rats, Sprague-Dawley males, and rats of both sexes of the Long-Evans lineage as well as male albino mice and C57BL females were included in the experiments. Studies showed that extracts of the fruit, the fresh fruit, or its various fractions had positive effects on the following markers: glycated hemoglobin, cholesterol, HOMA-IR, oral glucose tolerance test, and blood glucose, in acute (2 and 24 h), and chronic (up to 4 months) treatment. CONCLUSION An important hypoglycemic effect of okra in its various fractions on induced diabetes was observed by different authors. Moreover, okra promoted improvement in metabolic markers such as insulin sensitivity, lipid profile, and bodyweight loss.
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Affiliation(s)
- Aiane Benevide Sereno
- Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil.
| | - Carla Dayane Pinto
- Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil.
| | - Fabiana Antunes Andrade
- Laboratory of Molecular Immunopathology, Clinic Hospital, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil; Department of Medicine, Positive University (UP), R. Pedro Viriato Parigot de Souza, 5300, 81280-330, Curitiba, Paraná, Brazil.
| | - Michelli Aparecida Bertolazo da Silva
- Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil; Tuiuti University of Paraná (UTP), R. Sydnei Antonio Rangel Santos, 238 - Santo Inacio, 82010-330, Curitiba, Paraná, Brazil.
| | - Amanda Carvalho Garcia
- Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil.
| | - Cláudia Carneiro Hecke Krüger
- Postgraduate Program in Food and Nutrition, Federal University of Paraná (UFPR), Av. Lothário Meissner, 632, 80.210-170, Curitiba, Paraná, Brazil.
| | - Iara José de Messias Reason
- Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil; Laboratory of Molecular Immunopathology, Clinic Hospital, Federal University of Paraná (UFPR), R. Padre Camargo, 280, 80.069-900, Curitiba, Paraná, Brazil.
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Mukherjee A, Gaurav AK, Singh S, Yadav S, Bhowmick S, Abeysinghe S, Verma JP. The bioactive potential of phytohormones: A review. BIOTECHNOLOGY REPORTS (AMSTERDAM, NETHERLANDS) 2022; 35:e00748. [PMID: 35719852 PMCID: PMC9204661 DOI: 10.1016/j.btre.2022.e00748] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/31/2022] [Accepted: 06/07/2022] [Indexed: 11/04/2022]
Abstract
Phytohormones act as bioactive compound for plant, humans and microbes. Cytokinin, GA and auxin reduce reactive oxygen to prevent cancer & tumour disease. Phytohormones used in pharmaceuticals products and cosmetics for human. Microbes can be a potential source for plant hormones production. Phytohormones play a key role in signalling for plant-animal–microbe interactions. Plant hormones play an important role in growth, defence and plants productivity and there are several studies on their effects on plants. However, their role in humans and animals is limitedly studied. Recent studies suggest that plant hormone also works in mammalian systems, and have the potential to reduce human diseases such as cancer, diabetes, and also improve cell growth. Plant hormones such as indole-3-acetic acid (IAA) works as an antitumor, anti-cancer agent, gibberellins help in apoptosis, abscisic acid (ABA) as antidepressant compounds and regulation of glucose homeostasis whereas cytokinin works as an anti-ageing compound. The main aim of this review is to explore and correlate the relation of plant hormones and their important roles in animals, microbes and plants, and their interrelationships, emphasizing mainly human health. The most important and well-known plant hormones e.g., IAA, gibberellins, ABA, cytokinin and ethylene have been selected in this review to explore their effects on humans and animals.
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Affiliation(s)
- Arpan Mukherjee
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Anand Kumar Gaurav
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Saurabh Singh
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Shweta Yadav
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Shiuly Bhowmick
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
| | - Saman Abeysinghe
- Department of Botany, Faculty of Science, University of Ruhuna, Matara, Sri Lanka
| | - Jay Prakash Verma
- Institute of Environment and Sustainable Development, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
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Shabani M, Naderi R. Phytohormone abscisic acid elicits positive effects on harmaline-induced cognitive and motor disturbances in a rat model of essential tremor. Brain Behav 2022; 12:e2564. [PMID: 35591769 PMCID: PMC9120731 DOI: 10.1002/brb3.2564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 01/13/2022] [Accepted: 01/28/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE Essential tremor (ET) as a neurological disorder is accompanied by cognitive and motor disturbances. Despite the high incidence of ET, the drug treatment of ET remains unsatisfactory. Recently, abscisic acid (ABA) has been reported to have positive neurophysiological effects in mammals. Here, the effects of ABA on harmaline-induced motor and cognitive impairments were investigated in rats. METHODS Male Wistar rats weighing 120-140 g were divided into control, harmaline (30 mg/kg, ip), ABA vehicle (DMSO+normal saline), and ABA (10 μg/rat, icv, 30 min before harmaline injection) groups. Exploratory, balance and motor performance, anxiety, and cognitive function were assessed using footprint, open field, wire grip, rotarod, and shuttle box tests. RESULTS The results indicated that ABA (10 μg/rat) can improve harmaline-induced tremor in rats. The administration of ABA significantly increased time spent on wire grip and rotarod. In addition, ABA had a promising effect against the cognitive impairments induced by harmaline. CONCLUSION Taken together, ABA has positive effects on locomotor and cognitive impairments induced by tremor. However, further studies are required to determine the exact mechanisms of ABA on the ET.
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Affiliation(s)
- Mohammad Shabani
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
| | - Reyhaneh Naderi
- Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
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Huang W, Gu H, Zhan Z, Wang R, Song L, Zhang Y, Zhang Y, Li S, Li J, Zang Y, Li Y, Qian B. The plant hormone abscisic acid stimulates megakaryocyte differentiation from human iPSCs in vitro. Platelets 2021; 33:462-470. [PMID: 34223794 DOI: 10.1080/09537104.2021.1944616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
In the clinic, the supply of platelets is frequently insufficient to meet transfusion needs. To address this issue, many scientists have established the derivation of functional platelets from CD34+ cells or human pluripotent stem cells (PSCs). However, the yield of platelets is still far below what is required. Here we found that the plant hormone abscisic acid (ABA) could increase the generation of megakaryocytes (MKs) and platelets from human induced PSCs (hiPSCs). During platelet derivation, ABA treatment promoted the generation of CD34+/CD45+ HPCs and CD41+ MKs on day 14 and then increased CD41+/CD42b+ MKs and platelets on day 19. Moreover, we found ABA-mediated activation of Akt and ERK1/2 signal pathway through receptors LANCL2 and GRP78 in a PKA-dependent manner on CD34+/CD45+ cells. In conclusion, our data suggest that ABA treatment can promote CD34+/CD45+ HPC proliferation and CD41+ MK differentiation.
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Affiliation(s)
- Weihua Huang
- Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai China.,Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Haihui Gu
- Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai China
| | - Zhiyan Zhan
- Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Ruoru Wang
- Department of Neurology, The First Affiliated Hospital of Naval Medical University, Shanghai China
| | - Lili Song
- Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Yan Zhang
- Department of Hematology, The First Affiliated Hospital of Naval Medical University, Shanghai China
| | - Yingwen Zhang
- Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Shanshan Li
- Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Jinqi Li
- Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai China
| | - Yan Zang
- Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai China
| | - Yanxin Li
- Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai, China
| | - Baohua Qian
- Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai China
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13
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Zhou N, Wei Z, Qi Z, Chen L. Abscisic Acid-Induced Autophagy Selectively via MAPK/JNK Signalling Pathway in Glioblastoma. Cell Mol Neurobiol 2021; 41:813-826. [PMID: 32577848 PMCID: PMC7997842 DOI: 10.1007/s10571-020-00888-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 05/26/2020] [Indexed: 02/07/2023]
Abstract
As a widely known plant hormone, Abscisic acid plays an important role in the progress of planting cell and their stress response. Recently, we reported that ABA might play an anti-cancer role in glioma tissues. In the present study, the molecular mechanism of ABA anti-cancer was further explored in glioblastoma cells. By measuring LC3 puncta formation and conversion in glioblastoma cells, inhibiting the autophagic pathway, targeting the essential autophagic modulator beclin 1 with RNA interference, and analysing cellular morphology via transmission electron microscopy, we found that ABA-treated glioblastoma cells exhibited the features of autophagy. Specifically, ABA-induced autophagy in glioblastoma cells was mediated by the MAPK/JNK signalling pathway rather than the PI3K/AKT/mTOR axis. Moreover, the inhibition or knockdown of JNK specifically blocked ABA-induced autophagic cell death. ABA-induced autophagy was further confirmed in tumour-bearing mice and was accompanied by the inhibition of glioma growth in vivo. This report is the first to describe autophagy induced by ABA and mediated by the MAPK/JNK pathway in human cancer cells and tumour-bearing mice. These results may shed some light in new therapeutic strategies of glioma.
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Affiliation(s)
- Nan Zhou
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Zixuan Wei
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Zengxin Qi
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Liang Chen
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China.
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14
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Galgaro BC, Beckenkamp LR, van den M Nunnenkamp M, Korb VG, Naasani LIS, Roszek K, Wink MR. The adenosinergic pathway in mesenchymal stem cell fate and functions. Med Res Rev 2021; 41:2316-2349. [PMID: 33645857 DOI: 10.1002/med.21796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/02/2021] [Accepted: 02/17/2021] [Indexed: 12/18/2022]
Abstract
Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis and damage repair through their ability to differentiate into cells of different tissues, trophic support, and immunomodulation. These properties made them attractive for clinical applications in regenerative medicine, immune disorders, and cell transplantation. However, despite multiple preclinical and clinical studies demonstrating beneficial effects of MSCs, their native identity and mechanisms of action remain inconclusive. Since its discovery, the CD73/ecto-5'-nucleotidase is known as a classic marker for MSCs, but its role goes far beyond a phenotypic characterization antigen. CD73 contributes to adenosine production, therefore, is an essential component of purinergic signaling, a pathway composed of different nucleotides and nucleosides, which concentrations are finely regulated by the ectoenzymes and receptors. Thus, purinergic signaling controls pathophysiological functions such as proliferation, migration, cell fate, and immune responses. Despite the remarkable progress already achieved in considering adenosinergic pathway as a therapeutic target in different pathologies, its role is not fully explored in the context of the therapeutic functions of MSCs. Therefore, in this review, we provide an overview of the role of CD73 and adenosine-mediated signaling in the functions ascribed to MSCs, such as homing and proliferation, cell differentiation, and immunomodulation. Additionally, we will discuss the pathophysiological role of MSCs, via CD73 and adenosine, in different diseases, as well as in tumor development and progression. A better understanding of the adenosinergic pathway in the regulation of MSCs functions will help to provide improved therapeutic strategies applicable in regenerative medicine.
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Affiliation(s)
- Bruna C Galgaro
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Liziane R Beckenkamp
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Martha van den M Nunnenkamp
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Vitória G Korb
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Liliana I S Naasani
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
| | - Katarzyna Roszek
- Department of Biochemistry, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Toruń, Poland
| | - Márcia R Wink
- Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil
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15
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Jung Y, Cackowski FC, Yumoto K, Decker AM, Wang Y, Hotchkin M, Lee E, Buttitta L, Taichman RS. Abscisic acid regulates dormancy of prostate cancer disseminated tumor cells in the bone marrow. Neoplasia 2021; 23:102-111. [PMID: 33296752 PMCID: PMC7721692 DOI: 10.1016/j.neo.2020.11.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 11/11/2020] [Accepted: 11/16/2020] [Indexed: 01/26/2023]
Abstract
Prostate cancer (PCa) commonly metastasizes to the bone where the cells frequently undergo dormancy. The escape of disseminated tumor cells from cellular dormancy is a major cause of recurrence in marrow. Abscisic acid (ABA), a phytohormone, is known to regulate dormancy of plant seeds and to regulate other stress responses in plants. Recently, ABA was found to be synthesized by mammals cells and has been linked to human disease. Yet the role of ABA in regulating tumor dormancy or reactivation is unknown. We found that ABA is produced by human marrow cells, and exogenous ABA inhibits PCa cell proliferation while increasing the expression of p27, p21, and p16 and decreasing the expression of the proliferation marker, Ki67. Further, ABA significantly increased the percentage of PCa cells in the G0 phase of the cell cycle as well as the duration the cells were arrested in G0. We found that ABA regulates an increase of PPARγ receptor expression and suppressed phosphorylation of mTOR/p70S6K signaling and resulting in the induction of the cellular dormancy. We then confirmed that ABA regulates G0 cell cycle arrest through PPARγ receptor signaling in vitro and under co-culture conditions with osteoblasts. Finally, we demonstrate that ABA regulates PCa dormancy in vivo following intratibial injection in an animal model. Together these data suggest that the ABA and PPARγ signaling pathways contribute to the establishment of PCa cellular dormancy in the bone marrow microenvironment. These findings may suggest critical pathways for targeting metastatic disease.
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Affiliation(s)
- Younghun Jung
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Frank C Cackowski
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
| | - Kenji Yumoto
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Ann M Decker
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Yu Wang
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Megan Hotchkin
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Eunsohl Lee
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
| | - Laura Buttitta
- Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Russell S Taichman
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Department of Periodontics, University of Alabama at Birmingham, Birmingham, AL, USA.
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16
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Piedra-Quintero ZL, Wilson Z, Nava P, Guerau-de-Arellano M. CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Front Immunol 2020; 11:597959. [PMID: 33329591 PMCID: PMC7734206 DOI: 10.3389/fimmu.2020.597959] [Citation(s) in RCA: 168] [Impact Index Per Article: 33.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 11/02/2020] [Indexed: 12/13/2022] Open
Abstract
CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or as a receptor with adhesive functions. CD38 can be found expressed either on the cell surface, where it may face the extracellular milieu or the cytosol, or in intracellular compartments, such as endoplasmic reticulum, nuclear membrane, and mitochondria. The main expression of CD38 is observed in hematopoietic cells, with some cell-type specific differences between mouse and human. The role of CD38 in immune cells ranges from modulating cell differentiation to effector functions during inflammation, where CD38 may regulate cell recruitment, cytokine release, and NAD availability. In line with a role in inflammation, CD38 appears to also play a critical role in inflammatory processes during autoimmunity, although whether CD38 has pathogenic or regulatory effects varies depending on the disease, immune cell, or animal model analyzed. Given the complexity of the physiology of CD38 it has been difficult to completely understand the biology of this molecule during autoimmune inflammation. In this review, we analyze current knowledge and controversies regarding the role of CD38 during inflammation and autoimmunity and novel molecular tools that may clarify current gaps in the field.
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Affiliation(s)
- Zayda L. Piedra-Quintero
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
| | - Zachary Wilson
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
- Biomedical Science Undergraduate Program, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
| | - Porfirio Nava
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (CINVESTAV), México City, México
| | - Mireia Guerau-de-Arellano
- School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
- Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, United States
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States
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17
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Michiels M, Daleo G, López Mañanes A. Differential modulation after feeding in different salinities and response to abscisic acid (ABA) and extracellular Ca 2+ of aminopeptidase N (APN) activity in the hepatopancreas of the intertidal euryhaline crab Neohelice granulata. CAN J ZOOL 2020. [DOI: 10.1139/cjz-2019-0163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Modulation of aminopeptidase N (APN) activity in the digestive tract by various factors would be important to adjust digestive and absorptive processes under different physiological and (or) environmental conditions. We studied the postprandial responses at different salinities and the effect of abscisic acid (ABA) and extracellular Ca2+ on APN activity in the hepatopancreas (the main site for nutrient digestion and absorption) of the model species Neohelice granulata (Dana, 1851). Enzyme activity was determined at different times (0, 24, 48, and 72 h) after feeding in crabs acclimated either to 35 psu (osmoconformation) or 10 psu (hyper-regulation). APN activity increased around 50% at 24 h after feeding at 35 psu, whereas no changes occurred at 10 psu. Enzyme activity was also assayed in the presence of ABA (1 × 10–4 mol·L–1) or extracellular Ca2+ (1 × 10–4 mol·L–1), showing increments of 60% and 56%, respectively. The results suggest a role of APN in postprandial adjustments and its modulation by different chemical messengers by direct effect on the hepatopancreas. Moreover, to our knowledge, this work is the first to show the effect of ABA on a digestive enzyme in the digestive tract of an animal.
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Affiliation(s)
- M.S. Michiels
- Instituto de Investigaciones Marinas y Costeras (IIMyC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Mar del Plata, Funes 3250, Mar del Plata, Argentina
| | - G.R. Daleo
- Instituto de Investigaciones Biológicas (IIB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Mar del Plata, Mar del, Plata, Argentina
| | - A.A. López Mañanes
- Instituto de Investigaciones Marinas y Costeras (IIMyC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Mar del Plata, Funes 3250, Mar del Plata, Argentina
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18
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Daliu P, Annunziata G, Tenore GC, Santini A. Abscisic acid identification in Okra, Abelmoschus esculentus L. (Moench): perspective nutraceutical use for the treatment of diabetes. Nat Prod Res 2019; 34:3-9. [DOI: 10.1080/14786419.2019.1637874] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Patricia Daliu
- Department of Pharmacy, University of Napoli Federico II, Napoli, Italy
| | | | - Gian Carlo Tenore
- Department of Pharmacy, University of Napoli Federico II, Napoli, Italy
| | - Antonello Santini
- Department of Pharmacy, University of Napoli Federico II, Napoli, Italy
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19
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Khorasani A, Abbasnejad M, Esmaeili-Mahani S. Phytohormone abscisic acid ameliorates cognitive impairments in streptozotocin-induced rat model of Alzheimer's disease through PPARβ/δ and PKA signaling. Int J Neurosci 2019; 129:1053-1065. [PMID: 31215291 DOI: 10.1080/00207454.2019.1634067] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Aim: Alzheimer's disease (AD) is characterized by oxidative stress, neuroinflammation and progressive cognitive decline. Abscisic acid (ABA) is produced in a variety of mammalian tissues, including brain. It has anti-inflammatory and antioxidant effects and elicits a positive effect on spatial learning and memory performance. Here, the possible protective effect of ABA was evaluated in streptozotocin (STZ)-induced AD rat model which were injected intracerebroventriculary (i.c.v.) with STZ (3 mg/kg). Material and Methods: The STZ-treated animals received ABA (10 μg/rat, i.c.v.), ABA plus PPARβ/δ receptor antagonist (GSK0660, 80 nM/rat) or ABA plus selective inhibitor of PKA (KT5720, 0.5 μg/rat) for 14 d. Learning and memory were determined using Morris water maze (MWM) and passive avoidance (PA) tests. Results: The data showed that STZ produced a significant learning and memory deficit in both MWM and PA tests. ABA significantly prevented the learning and memory impairment in STZ-treated rats. However, ABA effects were blocked by GSK0660 and KT5720. Conclusion: The data indicated that ABA attenuates STZ-induced learning and memory impairment and PPAR-β/δ receptors and PKA signaling are involved, at least in part, in the ABA mechanism.
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Affiliation(s)
- Ali Khorasani
- Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman , Kerman , Iran.,Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC), Institute of neuropharmacology, Kerman University of Medical Sciences , Kerman , Iran
| | - Mehdi Abbasnejad
- Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman , Kerman , Iran.,Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC), Institute of neuropharmacology, Kerman University of Medical Sciences , Kerman , Iran
| | - Saeed Esmaeili-Mahani
- Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman , Kerman , Iran.,Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC), Institute of neuropharmacology, Kerman University of Medical Sciences , Kerman , Iran
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20
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Rafiepour K, Esmaeili-Mahani S, Salehzadeh A, Sheibani V. Phytohormone Abscisic Acid Protects Human Neuroblastoma SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity Through Its Antioxidant and Antiapoptotic Properties. Rejuvenation Res 2019; 22:99-108. [DOI: 10.1089/rej.2018.2062] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Kiana Rafiepour
- Department of Biology, Rasht Branch, Islamic Azad University. Rasht, Iran
| | - Saeed Esmaeili-Mahani
- Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
- Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Ali Salehzadeh
- Department of Biology, Rasht Branch, Islamic Azad University. Rasht, Iran
| | - Vahid Sheibani
- Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
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21
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Naderi R, Esmaeili-Mahani S, Abbasnejad M. Extracellular calcium influx through L-type calcium channels, intracellular calcium currents and extracellular signal-regulated kinase signaling are involved in the abscisic acid-induced precognitive and anti-anxiety effects. Biomed Pharmacother 2019; 109:582-588. [DOI: 10.1016/j.biopha.2018.10.141] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 10/14/2018] [Accepted: 10/24/2018] [Indexed: 10/27/2022] Open
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22
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Liu J, Gu X, Zou R, Nan W, Yang S, Wang HL, Chen XT. Phytohormone Abscisic Acid Improves Spatial Memory and Synaptogenesis Involving NDR1/2 Kinase in Rats. Front Pharmacol 2018; 9:1141. [PMID: 30356880 PMCID: PMC6190901 DOI: 10.3389/fphar.2018.01141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 09/19/2018] [Indexed: 11/13/2022] Open
Abstract
The abscisic acid (ABA) is a phytohormone involved in plant growth, development and environmental stress response. Recent study showed ABA can also be detected in other organisms, including mammals. And it has been reported that ABA can improve learning and memory in rats. In this study, we attempted to investigate the effects of ABA on the alternation of dendritic spine morphology of pyramidal neurons in developmental rats, which may underlie the learning and memory function. Behavior tests showed that ABA significantly improved spatial memory performance. Meanwhile, Golgi-Cox staining assay showed that ABA significantly increased the spine density and the percentage of mushroom-like spines in pyramidal neurons of hippocampus, indicating that ABA increased dendritic spine formation and maturation, which may contribute to the improvement of spatial memory. Furthermore, ABA administration increased the protein expression of NDR1/2 kinase, as well as mRNA levels of NDR2 and its substrate Rabin8. In addition, NDR1/2 shRNA prohibited the ABA-induced increases in the expression of NDR1/2 and spine density. Together, our study indicated that ABA could improve learning and memory in rats and the effect are possibly through the regulation of synaptogenesis, which is mediated via NDR1/2 kinase pathway.
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Affiliation(s)
- Juanjuan Liu
- School of Food Science and Engineering, Hefei University of Technology, Hefei, China
| | - Xiaozhen Gu
- School of Food Science and Engineering, Hefei University of Technology, Hefei, China
| | - Rongxin Zou
- School of Food Science and Engineering, Hefei University of Technology, Hefei, China
| | - Wenping Nan
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Shaohua Yang
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Hui-Li Wang
- School of Food Science and Engineering, Hefei University of Technology, Hefei, China
| | - Xiang-Tao Chen
- School of Pharmacy, Anhui Medical University, Hefei, China
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23
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Olds CL, Glennon EKK, Luckhart S. Abscisic acid: new perspectives on an ancient universal stress signaling molecule. Microbes Infect 2018; 20:484-492. [PMID: 29408537 DOI: 10.1016/j.micinf.2018.01.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 01/17/2018] [Accepted: 01/18/2018] [Indexed: 01/06/2023]
Abstract
Few biological molecules have as far reaching and dynamic effects as abscisic acid (ABA). In this review, we draw together the often segregated fields of plant, animal, and human biology to highlight ABA biosynthesis, signaling and physiological effects with examples of host-pathogen interactions to emphasize the cross-kingdom biology of this ancient signaling molecule.
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Affiliation(s)
- Cassandra L Olds
- Department of Entomology, Plant Pathology and Nematology, University of Idaho, 875 Perimeter Drive MS 2329, Moscow, ID, 83844-2329, USA; Center for Health in the Human Ecosystem, University of Idaho, 875 Perimeter Drive MS 1122, Moscow, ID, 83844-1122, USA.
| | - Elizabeth K K Glennon
- Center for Infectious Disease Research, 307 Westlake Ave N, Suite 500, Seattle, WA, 98109, USA
| | - Shirley Luckhart
- Department of Entomology, Plant Pathology and Nematology, University of Idaho, 875 Perimeter Drive MS 2329, Moscow, ID, 83844-2329, USA; Center for Health in the Human Ecosystem, University of Idaho, 875 Perimeter Drive MS 1122, Moscow, ID, 83844-1122, USA; Department of Biological Sciences, University of Idaho 875 Perimeter Drive, MS 3051, Moscow, ID, 83844-3051, USA
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24
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Specific cyclic ADP-ribose phosphohydrolase obtained by mutagenic engineering of Mn 2+-dependent ADP-ribose/CDP-alcohol diphosphatase. Sci Rep 2018; 8:1036. [PMID: 29348648 PMCID: PMC5773619 DOI: 10.1038/s41598-017-18393-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 12/12/2017] [Indexed: 01/16/2023] Open
Abstract
Cyclic ADP-ribose (cADPR) is a messenger for Ca2+ mobilization. Its turnover is believed to occur by glycohydrolysis to ADP-ribose. However, ADP-ribose/CDP-alcohol diphosphatase (ADPRibase-Mn) acts as cADPR phosphohydrolase with much lower efficiency than on its major substrates. Recently, we showed that mutagenesis of human ADPRibase-Mn at Phe37, Leu196 and Cys253 alters its specificity: the best substrate of the mutant F37A + L196F + C253A is cADPR by a short difference, Cys253 mutation being essential for cADPR preference. Its proximity to the 'northern' ribose of cADPR in docking models indicates Cys253 is a steric constraint for cADPR positioning. Aiming to obtain a specific cADPR phosphohydrolase, new mutations were tested at Asp250, Val252, Cys253 and Thr279, all near the 'northern' ribose. First, the mutant F37A + L196F + C253G, with a smaller residue 253 (Ala > Gly), showed increased cADPR specificity. Then, the mutant F37A + L196F + V252A + C253G, with another residue made smaller (Val > Ala), displayed the desired specificity, with cADPR kcat/KM ≈20-200-fold larger than for any other substrate. When tested in nucleotide mixtures, cADPR was exhausted while others remained unaltered. We suggest that the specific cADPR phosphohydrolase, by cell or organism transgenesis, or the designed mutations, by genome editing, provide opportunities to study the effect of cADPR depletion on the many systems where it intervenes.
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Naderi R, Esmaeili-Mahani S, Abbasnejad M. Phosphatidylinositol-3-kinase and protein kinase C are involved in the pro-cognitive and anti-anxiety effects of phytohormone abscisic acid in rats. Biomed Pharmacother 2017; 96:112-119. [DOI: 10.1016/j.biopha.2017.09.089] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 09/17/2017] [Accepted: 09/18/2017] [Indexed: 11/26/2022] Open
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Kotova PD, Bystrova MF, Rogachevskaja OA, Khokhlov AA, Sysoeva VY, Tkachuk VA, Kolesnikov SS. Coupling of P2Y receptors to Ca 2+ mobilization in mesenchymal stromal cells from the human adipose tissue. Cell Calcium 2017; 71:1-14. [PMID: 29604959 DOI: 10.1016/j.ceca.2017.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 10/25/2017] [Accepted: 11/06/2017] [Indexed: 12/19/2022]
Abstract
The purinergic transduction was examined in mesenchymal stromal cells (MSCs) from the human adipose tissue, and several nucleotides, including ATP, UTP, and ADP, were found to mobilize cytosolic Ca2+. Transcripts for multiple purinoreceptors were detected in MSC preparations, including A1, A2A, A2B, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y13, P2Y14, P2X2, P2X4, and P2X7. Cellular responses to nucleotides were insignificantly sensitive to bath Ca2+, pointing at a minor contribution of Ca2+ entry, and were suppressed by U73122 and 2-APB, implicating the phosphoinositide cascade in coupling P2Y receptors to Ca2+ release. While individual cells were sensitive to several P2Y agonists, responsiveness to a given nucleotide varied from cell to cell, suggesting that particular MSCs could employ different sets of purinoreceptors. Caged Ca2+ stimulated Ca2+-induced Ca2+ release (CICR) that was mediated largely by IP3 receptors, and resultant Ca2+ transients were similar to nucleotide responses by magnitude and kinetics. A variety of findings hinted at CICR to be a universal mechanism that finalizes Ca2+ signaling initiated by agonists in MSCs. Individual MSCs responded to nucleotides in an all-or-nothing manner. Presumably just CICR provided invariant Ca2+ responses observed in MSCs at different nucleotide concentrations. The effects of isoform specific agonists and antagonists suggested that both P2Y1 and P2Y13 were obligatory for ADP responses, while P2Y4 and P2Y11 served as primary UTP and ATP receptors, respectively. Extracellular NAD+ stimulated Ca2+ signaling in each ATP-responsive MSC by involving P2Y11. The overall data indicate that extracellular nucleotides and NAD+ can serve as autocrine/paracrine factors regulating MSC functions.
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Affiliation(s)
- Polina D Kotova
- Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia
| | - Marina F Bystrova
- Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia
| | - Olga A Rogachevskaja
- Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia
| | - Alexander A Khokhlov
- Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia
| | - Veronika Yu Sysoeva
- Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia
| | - Vsevolod A Tkachuk
- Department of Biochemistry and Molecular Medicine, Faculty of Basic Medicine, Lomonosov Moscow State University, Russia
| | - Stanislav S Kolesnikov
- Institute of Cell Biophysics, Russian Academy of Sciences, Institutional Street 3, Pushchino, Moscow Region, 142290, Russia.
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Zocchi E, Hontecillas R, Leber A, Einerhand A, Carbo A, Bruzzone S, Tubau-Juni N, Philipson N, Zoccoli-Rodriguez V, Sturla L, Bassaganya-Riera J. Abscisic Acid: A Novel Nutraceutical for Glycemic Control. Front Nutr 2017; 4:24. [PMID: 28660193 PMCID: PMC5468461 DOI: 10.3389/fnut.2017.00024] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 05/19/2017] [Indexed: 01/03/2023] Open
Abstract
Abscisic acid is naturally present in fruits and vegetables, and it plays an important role in managing glucose homeostasis in humans. According to the latest U.S. dietary survey, about 92% of the population might have a deficient intake of ABA due to their deficient intake of fruits and vegetables. This review summarizes the in vitro, preclinical, mechanistic, and human translational findings obtained over the past 15 years in the study of the role of ABA in glycemic control. In 2007, dietary ABA was first reported to ameliorate glucose tolerance and obesity-related inflammation in mice. The most recent findings regarding the topic of ABA and its proposed receptor lanthionine synthetase C-like 2 in glycemic control and their interplay with insulin and glucagon-like peptide-1 suggest a major role for ABA in the physiological response to a glucose load in humans. Moreover, emerging evidence suggests that the ABA response might be dysfunctional in diabetic subjects. Follow on intervention studies in healthy individuals show that low-dose dietary ABA administration exerts a beneficial effect on the glycemia and insulinemia profiles after oral glucose load. These recent findings showing benefits in humans, together with extensive efficacy data in mouse models of diabetes and inflammatory disease, suggest the need for reference ABA values and its possible exploitation of the glycemia-lowering effects of ABA for preventative purposes. Larger clinical studies on healthy, prediabetic, and diabetic subjects are needed to determine whether addressing the widespread dietary ABA deficiency improves glucose control in humans.
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Affiliation(s)
- Elena Zocchi
- Department of Experimental Medicine, Section of Biochemistry and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
| | - Raquel Hontecillas
- BioTherapeutics Inc., Blacksburg, VA, United States.,Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States
| | - Andrew Leber
- BioTherapeutics Inc., Blacksburg, VA, United States
| | | | - Adria Carbo
- BioTherapeutics Inc., Blacksburg, VA, United States
| | - Santina Bruzzone
- Department of Experimental Medicine, Section of Biochemistry and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
| | - Nuria Tubau-Juni
- Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States
| | | | | | - Laura Sturla
- Department of Experimental Medicine, Section of Biochemistry and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
| | - Josep Bassaganya-Riera
- BioTherapeutics Inc., Blacksburg, VA, United States.,Nutritional Immunology and Molecular Medicine Laboratory, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, United States
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28
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Sturla L, Mannino E, Scarfì S, Bruzzone S, Magnone M, Sociali G, Booz V, Guida L, Vigliarolo T, Fresia C, Emionite L, Buschiazzo A, Marini C, Sambuceti G, De Flora A, Zocchi E. Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo. Biochim Biophys Acta Mol Cell Biol Lipids 2017; 1862:131-144. [PMID: 27871880 DOI: 10.1016/j.bbalip.2016.11.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 10/20/2016] [Accepted: 11/14/2016] [Indexed: 11/30/2022]
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29
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Malara A, Fresia C, Di Buduo CA, Soprano PM, Moccia F, Balduini C, Zocchi E, De Flora A, Balduini A. The Plant Hormone Abscisic Acid Is a Prosurvival Factor in Human and Murine Megakaryocytes. J Biol Chem 2017; 292:3239-3251. [PMID: 28049729 DOI: 10.1074/jbc.m116.751693] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 12/23/2016] [Indexed: 11/06/2022] Open
Abstract
Abscisic acid (ABA) is a phytohormone involved in pivotal physiological functions in higher plants. Recently, ABA has been proven to be also secreted and active in mammals, where it stimulates the activity of innate immune cells, mesenchymal and hematopoietic stem cells, and insulin-releasing pancreatic β cells through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). In addition to behaving like an animal hormone, ABA also holds promise as a nutraceutical plant-derived compound in humans. Many biological functions of ABA in mammals are mediated by its binding to the LANCL-2 receptor protein. A putative binding of ABA to GRP78, a key regulator of endoplasmic reticulum stress, has also been proposed. Here we investigated the role of exogenous ABA in modulating thrombopoiesis, the process of platelet generation. Our results demonstrate that expression of both LANCL-2 and GRP78 is up-regulated during hematopoietic stem cell differentiation into mature megakaryocytes (Mks). Functional ABA receptors exist in mature Mks because ABA induces an intracellular Ca2+ increase ([Ca2+] i ) through PKA activation and subsequent cADPR generation. In vitro exposure of human or murine hematopoietic progenitor cells to 10 μm ABA does not increase recombinant thrombopoietin (rTpo)-dependent Mk differentiation or platelet release. However, under conditions of cell stress induced by rTpo and serum deprivation, ABA stimulates, in a PKA- and cADPR-dependent fashion, the mitogen-activated kinase ERK 1/2, resulting in the modulation of lymphoma 2 (Bcl-2) family members, increased Mk survival, and higher rates of platelet production. In conclusion, we demonstrate that ABA is a prosurvival factor for Mks in a Tpo-independent manner.
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Affiliation(s)
- Alessandro Malara
- Departments of Molecular Medicine, Laboratories of Biotechnology, IRCCS San Matteo Foundation
| | - Chiara Fresia
- Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova 16132, Italy
| | | | - Paolo Maria Soprano
- Departments of Molecular Medicine, Laboratories of Biotechnology, IRCCS San Matteo Foundation
| | - Francesco Moccia
- Biology and Biotechnology, University of Pavia, Pavia 27100, Italy
| | - Cesare Balduini
- Biology and Biotechnology, University of Pavia, Pavia 27100, Italy
| | - Elena Zocchi
- Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova 16132, Italy
| | - Antonio De Flora
- Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova 16132, Italy
| | - Alessandra Balduini
- Departments of Molecular Medicine, Laboratories of Biotechnology, IRCCS San Matteo Foundation; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155.
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Lievens L, Pollier J, Goossens A, Beyaert R, Staal J. Abscisic Acid as Pathogen Effector and Immune Regulator. FRONTIERS IN PLANT SCIENCE 2017; 8:587. [PMID: 28469630 PMCID: PMC5395610 DOI: 10.3389/fpls.2017.00587] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 03/31/2017] [Indexed: 05/18/2023]
Abstract
Abscisic acid (ABA) is a sesquiterpene signaling molecule produced in all kingdoms of life. To date, the best known functions of ABA are derived from its role as a major phytohormone in plant abiotic stress resistance. Different organisms have developed different biosynthesis and signal transduction pathways related to ABA. Despite this, there are also intriguing common themes where ABA often suppresses host immune responses and is utilized by pathogens as an effector molecule. ABA also seems to play an important role in compatible mutualistic interactions such as mycorrhiza and rhizosphere bacteria with plants, and possibly also the animal gut microbiome. The frequent use of ABA in inter-species communication could be a possible reason for the wide distribution and re-invention of ABA as a signaling molecule in different organisms. In humans and animal models, it has been shown that ABA treatment or nutrient-derived ABA is beneficial in inflammatory diseases like colitis and type 2 diabetes, which confer potential to ABA as an interesting nutraceutical or pharmacognostic drug. The anti-inflammatory activity, cellular metabolic reprogramming, and other beneficial physiological and psychological effects of ABA treatment in humans and animal models has sparked an interest in this molecule and its signaling pathway as a novel pharmacological target. In contrast to plants, however, very little is known about the ABA biosynthesis and signaling in other organisms. Genes, tools and knowledge about ABA from plant sciences and studies of phytopathogenic fungi might benefit biomedical studies on the physiological role of endogenously generated ABA in humans.
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Affiliation(s)
- Laurens Lievens
- Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, VIBGhent, Belgium
- Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium
| | - Jacob Pollier
- VIB-UGent Center for Plant Systems Biology, VIBGhent, Belgium
- Department of Plant Biotechnology and Bioinformatics, Ghent UniversityGhent, Belgium
| | - Alain Goossens
- VIB-UGent Center for Plant Systems Biology, VIBGhent, Belgium
- Department of Plant Biotechnology and Bioinformatics, Ghent UniversityGhent, Belgium
| | - Rudi Beyaert
- Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, VIBGhent, Belgium
- Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium
| | - Jens Staal
- Unit of Molecular Signal Transduction in Inflammation, VIB-UGent Center for Inflammation Research, VIBGhent, Belgium
- Department of Biomedical Molecular Biology, Ghent UniversityGhent, Belgium
- *Correspondence: Jens Staal
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31
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Jiao C, Yang R, Gu Z. Cyclic ADP-ribose and IP3 mediate abscisic acid-induced isoflavone accumulation in soybean sprouts. Biochem Biophys Res Commun 2016; 479:530-536. [PMID: 27664703 DOI: 10.1016/j.bbrc.2016.09.104] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 09/20/2016] [Indexed: 10/21/2022]
Abstract
In this study, the roles of ABA-cADPR-Ca2+ and ABA-IP3-Ca2+ signaling pathways in UV-B-induced isoflavone accumulation in soybean sprouts were investigated. Results showed that abscisic acid (ABA) up regulated cyclic ADP-ribose (cADPR) and inositol 1,4,5-trisphosphate (IP3) levels in soybean sprouts under UV-B radiation. Furthermore, cADPR and IP3, as second messengers of UV-B-triggered ABA, induced isoflavone accumulation by up-regulating proteins and genes expression and activity of isoflavone biosynthetic-enzymes (chalcone synthase, CHS; isoflavone synthase, IFS). After Ca2+ was chelated by EGTA, isoflavone content decreased. Overall, ABA-induced cADPR and IP3 up regulated isoflavone accumulation which was mediated by Ca2+ signaling via enhancing the expression of proteins and genes participating in isoflavone biosynthesis in soybean sprouts under UV-B radiation.
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Affiliation(s)
- Caifeng Jiao
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, People's Republic of China
| | - Runqiang Yang
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, People's Republic of China
| | - Zhenxin Gu
- College of Food Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, People's Republic of China.
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32
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G-protein coupling and nuclear translocation of the human abscisic acid receptor LANCL2. Sci Rep 2016; 6:26658. [PMID: 27222287 PMCID: PMC4879523 DOI: 10.1038/srep26658] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Accepted: 04/27/2016] [Indexed: 02/03/2023] Open
Abstract
Abscisic acid (ABA), a long known phytohormone, has been recently demonstrated to be present also in humans, where it targets cells of the innate immune response, mesenchymal and hemopoietic stem cells and cells involved in the regulation of systemic glucose homeostasis. LANCL2, a peripheral membrane protein, is the mammalian ABA receptor. We show that N-terminal glycine myristoylation causes LANCL2 localization to the plasmamembrane and to cytoplasmic membrane vesicles, where it interacts with the α subunit of a Gi protein and starts the ABA signaling pathway via activation of adenylate cyclase. Demyristoylation of LANCL2 by chemical or genetic means triggers its nuclear translocation. Nuclear enrichment of native LANCL2 is also induced by ABA treatment. Therefore human LANCL2 is a non-transmembrane G protein-coupled receptor susceptible to hormone-induced nuclear translocation.
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33
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Abscisic acid influx into human nucleated cells occurs through the anion exchanger AE2. Int J Biochem Cell Biol 2016; 75:99-103. [PMID: 27015766 DOI: 10.1016/j.biocel.2016.03.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 02/09/2016] [Accepted: 03/17/2016] [Indexed: 11/24/2022]
Abstract
Abscisic acid (ABA) is a hormone conserved from cyanobacteria to higher plants, where it regulates responses to environmental stimuli. ABA also plays a role in mammalian physiology, pointedly in inflammatory responses and in glycemic control. As the animal ABA receptor is on the intracellular side of the plasma membrane, a transporter is required for the hormone's action. Here we demonstrate that ABA transport in human nucleated cells occurs via the anion exchanger AE2. Together with the recent demonstration that ABA influx into human erythrocytes occurs via Band 3, this result identifies the AE family members as the mammalian ABA transporters.
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34
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Glennon EKK, Adams LG, Hicks DR, Dehesh K, Luckhart S. Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission. Am J Trop Med Hyg 2016; 94:1266-75. [PMID: 27001761 DOI: 10.4269/ajtmh.15-0904] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Accepted: 01/29/2016] [Indexed: 01/20/2023] Open
Abstract
Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.
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Affiliation(s)
- Elizabeth K K Glennon
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California
| | - L Garry Adams
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California
| | - Derrick R Hicks
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California
| | - Katayoon Dehesh
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California
| | - Shirley Luckhart
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California; Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Plant Biology, University of California, Davis, Davis, California
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Zhou N, Yao Y, Ye H, Zhu W, Chen L, Mao Y. Abscisic-acid-induced cellular apoptosis and differentiation in glioma via the retinoid acid signaling pathway. Int J Cancer 2015; 138:1947-58. [PMID: 26594836 DOI: 10.1002/ijc.29935] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 11/10/2015] [Indexed: 12/15/2022]
Abstract
Retinoid acid (RA) plays critical roles in regulating differentiation and apoptosis in a variety of cancer cells. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share structural similarities. Here we proposed that ABA may also play a role in cellular differentiation and apoptosis by sharing a similar signaling pathway with RA that may be involved in glioma pathogenesis. We reported for the first time that the ABA levels were twofold higher in low-grade gliomas compared with high-grade gliomas. In glioma tissues, there was a positive correlation between the ABA levels and the transcription of cellular retinoic acid-binding protein 2 (CRABP2) and a negative correlation between the ABA levels and transcription of fatty acid-binding protein 5 (FABP5). ABA treatment induced a significant increase in the expression of CRABP2 and a decrease in the expression of peroxisome proliferator-activated receptor (PPAR) in glioblastoma cells. Remarkably, both cellular apoptosis and differentiation were increased in the glioblastoma cells after ABA treatment. ABA-induced cellular apoptosis and differentiation were significantly reduced by selectively silencing RAR-α, while RAR-α overexpression exaggerated the ABA-induced effects. These results suggest that ABA may play a role in the pathogenesis of glioma by promoting cellular apoptosis and differentiation through the RA signaling pathway.
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Affiliation(s)
- Nan Zhou
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Yu Yao
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Hongxing Ye
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Wei Zhu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Liang Chen
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
| | - Ying Mao
- Department of Neurosurgery, Huashan Hospital, Fudan University, Middle Urumqi Road 12, Shanghai, 200040, China
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Magnone M, Ameri P, Salis A, Andraghetti G, Emionite L, Murialdo G, De Flora A, Zocchi E. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans. FASEB J 2015; 29:4783-93. [DOI: 10.1096/fj.15-277731] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 07/20/2015] [Indexed: 11/11/2022]
Affiliation(s)
- Mirko Magnone
- Department of Experimental MedicineSection of Biochemistry and Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
| | - Pietro Ameri
- Department of Internal MedicineUniversity of GenoaGenoaItaly
| | - Annalisa Salis
- Department of Experimental MedicineSection of Biochemistry and Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
| | | | - Laura Emionite
- Animal Facility, Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria San Martino, Istituto Scientifico TumoriGenoaItaly
| | | | - Antonio De Flora
- Department of Experimental MedicineSection of Biochemistry and Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
| | - Elena Zocchi
- Department of Experimental MedicineSection of Biochemistry and Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
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37
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Vigliarolo T, Guida L, Millo E, Fresia C, Turco E, De Flora A, Zocchi E. Abscisic acid transport in human erythrocytes. J Biol Chem 2015; 290:13042-52. [PMID: 25847240 DOI: 10.1074/jbc.m114.629501] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Indexed: 11/06/2022] Open
Abstract
Abscisic acid (ABA) is a plant hormone involved in the response to environmental stress. Recently, ABA has been shown to be present and active also in mammals, where it stimulates the functional activity of innate immune cells, of mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic β-cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane protein that localizes at the intracellular side of the plasma membrane. Here we investigated the mechanism enabling ABA transport across the plasmamembrane of human red blood cells (RBC). Both influx and efflux of [(3)H]ABA occur across intact RBC, as detected by radiometric and chromatographic methods. ABA binds specifically to Band 3 (the RBC anion transporter), as determined by labeling of RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human purified Band 3 transport [(3)H]ABA and [(35)S]sulfate, and ABA transport is sensitive to the specific Band 3 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2-mediated activation of adenylate cyclase. As ATP released from RBC is known to exert a vasodilator response, these results suggest a role for plasma ABA in the regulation of vascular tone.
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Affiliation(s)
- Tiziana Vigliarolo
- From the Department of Experimental Medicine, Section of Biochemistry, and
| | - Lucrezia Guida
- From the Department of Experimental Medicine, Section of Biochemistry, and
| | - Enrico Millo
- the Center of Excellence for Biomedical Research, University of Genova, Genova 16132, Italy and
| | - Chiara Fresia
- From the Department of Experimental Medicine, Section of Biochemistry, and
| | - Emilia Turco
- the Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10126, Italy
| | - Antonio De Flora
- From the Department of Experimental Medicine, Section of Biochemistry, and
| | - Elena Zocchi
- From the Department of Experimental Medicine, Section of Biochemistry, and
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38
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Qi CC, Zhang Z, Fang H, Liu J, Zhou N, Ge JF, Chen FH, Xiang CB, Zhou JN. Antidepressant effects of abscisic acid mediated by the downregulation of corticotrophin-releasing hormone gene expression in rats. Int J Neuropsychopharmacol 2014; 18:pyu006. [PMID: 25552429 PMCID: PMC4360223 DOI: 10.1093/ijnp/pyu006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Corticotrophin-releasing hormone (CRH) is considered to be the central driving force of the hypothalamic-pituitary-adrenal axis, which plays a key role in the stress response and depression. Clinical reports have suggested that excess retinoic acid (RA) is associated with depression. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share a similar molecular structure. Here, we proposed that ABA also plays a role in the regulation of CRH activity sharing with the RA signaling pathway. METHODS [3H]-ABA radioimmunoassay demonstrated that the hypothalamus of rats shows the highest concentration of ABA compared with the cortex and the hippocampus under basal conditions. RESULTS Under acute stress, ABA concentrations increased in the serum, but decreased in the hypothalamus and were accompanied by increased corticosterone in the serum and c-fos expression in the hypothalamus. Moreover, chronic ABA administration increased sucrose intake and decreased the mRNA expression of CRH and retinoic acid receptor alpha (RARα) in the hypothalamus of rats. Furthermore, ABA improved the symptom of chronic unpredictable mild stress in model rats, as indicated by increased sucrose intake, increased swimming in the forced swim test, and reduced mRNA expression of CRH and RARα in the rat hypothalamus. In vitro, CRH expression decreased after ABA treatment across different neural cells. In BE(2)-C cells, ABA inhibited a series of retinoid receptor expression, including RARα, a receptor that could facilitate CRH expression directly. CONCLUSIONS These results suggest that ABA may play a role in the pathogenesis of depression by downregulating CRH mRNA expression shared with the RA signaling pathway.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Jiang-Ning Zhou
- CAS Key Laboratory of Brain Function and Diseases, Schol of Life Science, University of Science and Technology of China, Anhui, China (Drs Qi, Zhang, Fang, Liu, Ge, Chen, and J-N Zhou); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (Dr N Zhou); Plant Molecular Biology Laboratory, School of Life Science, University of Science and Technology of China, Anhui, China (Dr Xiang).
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Preliminary evidence that abscisic acid improves spatial memory in rats. Physiol Behav 2014; 139:231-9. [PMID: 25449403 DOI: 10.1016/j.physbeh.2014.11.053] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Revised: 11/13/2014] [Accepted: 11/14/2014] [Indexed: 01/22/2023]
Abstract
Abscisic acid (ABA) is a crucial phytohormone that exists in a wide range of animals, including humans, and has multiple bioactivities. As direct derivatives of carotenoids, ABA and retinoic acid (RA) share similar molecular structures, and RA has been reported to improve spatial memory in rodents. To explore the potential effects of ABA on spatial learning and memory in rodents, 20mg/kg ABA was administered to young rats for 6weeks, and its effects on behaviour performance were evaluated through a series of behavioural tests. ABA pharmacokinetic analysis revealed that the exogenous ABA was distributed widely in the rat brain, characterised by rapid absorption and slow elimination. The behavioural tests showed that ABA increased both the duration spent in the target quadrant and the frequency it was entered in the probe test of the Morris water maze (MWM) and decreased the latency to locate the target quadrant. Moreover, ABA decreased the latency to enter the novel arm in the Y-maze test, accompanied by increases in the total entries and distance travelled in the three arms. However, there were no significant differences between the ABA-treated and control rats in the open field test and elevated plus-maze test. These results preliminarily indicate that ABA improves spatial memory in MWM and exploratory activity in Y-maze in young rats.
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Scarfì S. Purinergic receptors and nucleotide processing ectoenzymes: Their roles in regulating mesenchymal stem cell functions. World J Stem Cells 2014; 6:153-162. [PMID: 24772242 PMCID: PMC3999773 DOI: 10.4252/wjsc.v6.i2.153] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 02/10/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Human mesenchymal stem cells (MSCs) are a rare population of non-hematopoietic stem cells with multilineage potential, originally identified in the bone marrow. Due to the lack of a single specific marker, MSCs can be recognized and isolated by a series of features such as plastic adherence, a panel of surface markers, the clonogenic and the differentiation abilities. The recognized role of MSCs in the regulation of hemopoiesis, in cell-degeneration protection and in the homeostasis of mesodermal tissues through their differentiation properties, justifies the current interest in identifying the biochemical signals produced by MSCs and their active crosstalk in tissue environments. Only recently have extracellular nucleotides (eNTPs) and their metabolites been included among the molecular signals produced by MSCs. These molecules are active on both ionotropic and metabotropic receptors present in most cell types. MSCs possess a significant display of these receptors and of nucleotide processing ectoenzymes on their plasma membrane. Thus, from their niche, MSCs give a significant contribution to the complex signaling network of eNTPs and its derivatives. Recent studies have demonstrated the multifaceted aspects of eNTP metabolism and their signal transduction in MSCs and revealed important roles in specifying differentiation lineages and modulating MSC physiology and communication with other cells. This review discusses the roles of eNTPs, their receptors and ectoenzymes, and the relevance of the signaling network and MSC functions, and also focuses on the importance of this emerging area of interest for future MSC-based cell therapies.
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Wei W, Graeff R, Yue J. Roles and mechanisms of the CD38/cyclic adenosine diphosphate ribose/Ca 2+ signaling pathway. World J Biol Chem 2014; 5:58-67. [PMID: 24600514 PMCID: PMC3942542 DOI: 10.4331/wjbc.v5.i1.58] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 11/09/2013] [Accepted: 12/19/2013] [Indexed: 02/05/2023] Open
Abstract
Mobilization of intracellular Ca2+ stores is involved in many diverse cell functions, including: cell proliferation; differentiation; fertilization; muscle contraction; secretion of neurotransmitters, hormones and enzymes; and lymphocyte activation and proliferation. Cyclic adenosine diphosphate ribose (cADPR) is an endogenous Ca2+ mobilizing nucleotide present in many cell types and species, from plants to animals. cADPR is formed by ADP-ribosyl cyclases from nicotinamide adenine dinucleotide. The main ADP-ribosyl cyclase in mammals is CD38, a multi-functional enzyme and a type II membrane protein. It has been shown that many extracellular stimuli can induce cADPR production that leads to calcium release or influx, establishing cADPR as a second messenger. cADPR has been linked to a wide variety of cellular processes, but the molecular mechanisms regarding cADPR signaling remain elusive. The aim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advances involving the mechanism and physiological functions of cADPR-mediated Ca2+ mobilization.
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Grozio A, Gonzalez VM, Millo E, Sturla L, Vigliarolo T, Bagnasco L, Guida L, D'Arrigo C, De Flora A, Salis A, Martin EM, Bellotti M, Zocchi E. Selection and characterization of single stranded DNA aptamers for the hormone abscisic Acid. Nucleic Acid Ther 2013; 23:322-31. [PMID: 23971905 PMCID: PMC3760064 DOI: 10.1089/nat.2013.0418] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The hormone abscisic acid (ABA) is a small molecule involved in pivotal physiological functions in higher plants. Recently, ABA has been also identified as an endogenous hormone in mammals, regulating different cell functions including inflammatory processes, stem cell expansion, insulin release, and glucose uptake. Aptamers are short, single-stranded (ss) oligonucleotidesable to recognize target molecules with high affinity. The small size of the ABA molecule represented a challenge for aptamer development and the aim of this study was to develop specific anti-ABA DNA aptamers. Biotinylated abscisic acid (bio-ABA) was immobilized on streptavidin-coated magnetic beads. DNA aptamers against bio-ABA were selected with 7 iterative rounds of the systematic evolution of ligands by exponential enrichment method (SELEX), each round comprising incubation of the ABA-binding beads with the ssDNA sequences, DNA elution, electrophoresis, and polymerase chain reaction (PCR) amplification. The PCR product was cloned and sequenced. The binding affinity of several clones was determined using bio-ABA immobilized on streptavidin-coated plates. Aptamer 2 and aptamer 9 showed the highest binding affinity, with dissociation constants values of 0.98 ± 0.14 μM and 0.80 ± 0.07 μM, respectively. Aptamers 2 and 9 were also able to bind free, unmodified ABA and to discriminate between different ABA enantiomers and isomers. Our findings indicate that ssDNA aptamers can selectively bind ABA and could be used for the development of ABA quantitation assays.
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Affiliation(s)
- Alessia Grozio
- Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova, Italy
| | - Victor M. Gonzalez
- Departamento de Bioquímica-Investigación, IRYCIS-Hospital Ramón y Cajal, Madrid, Spain
| | - Enrico Millo
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Laura Sturla
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Tiziana Vigliarolo
- Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova, Italy
| | - Luca Bagnasco
- Department of Internal Medicine, University of Genova, Genova, Italy
| | - Lucrezia Guida
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Cristina D'Arrigo
- Institute for Macromolecular Studies, National Research Council, Genova, Italy
| | - Antonio De Flora
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Annalisa Salis
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Elena M. Martin
- Departamento de Bioquímica-Investigación, IRYCIS-Hospital Ramón y Cajal, Madrid, Spain
| | - Marta Bellotti
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
| | - Elena Zocchi
- Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy
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Tossi V, Cassia R, Bruzzone S, Zocchi E, Lamattina L. ABA says NO to UV-B: a universal response? TRENDS IN PLANT SCIENCE 2012; 17:510-7. [PMID: 22698377 DOI: 10.1016/j.tplants.2012.05.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 04/24/2012] [Accepted: 05/03/2012] [Indexed: 05/21/2023]
Abstract
Abscisic acid (ABA) signaling pathways have been widely characterized in plants, whereas the function of ABA in animals is less well understood. However, recent advances show ABA production by a wide range of lower animals and higher mammals. This enables a new evaluation of ABA signaling pathways in different organisms in response to common environmental stress, such as ultraviolet (UV)-B. In this opinion article, we propose that the induction of common signaling components, such as ABA, nitric oxide (NO) and Ca(2+), in plant and animal cells in response to high doses of UV-B, suggests that the evolution of a general mechanism activated by UV-B is conserved in divergent multicellular organisms challenged by a changing common environment.
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Affiliation(s)
- Vanesa Tossi
- Instituto de Investigaciones Biológicas, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Mar del Plata, Argentina
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Shinde S, Nurul Islam M, Ng CKY. Dehydration stress-induced oscillations in LEA protein transcripts involves abscisic acid in the moss, Physcomitrella patens. THE NEW PHYTOLOGIST 2012; 195:321-328. [PMID: 22591374 DOI: 10.1111/j.1469-8137.2012.04193.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
• Physcomitrella patens is a bryophyte belonging to early diverging lineages of land plants following colonization of land in the Ordovician period. Mosses are typically found in refugial habitats and can experience rapidly fluctuating environmental conditions. The acquisition of dehydration tolerance by bryophytes is of fundamental importance as they lack water-conducting tissues and are generally one cell layer thick. • Here, we show that dehydration induced oscillations in the steady-state transcript abundances of two group 3 late embryogenesis abundant (LEA) protein genes in P. patens protonemata, and that the amplitudes of these oscillations are reflective of the severity of dehydration stress. • Dehydration stress also induced elevations in the concentrations of abscisic acid (ABA), and ABA alone can also induce dosage-dependent oscillatory increases in the steady-state abundance of LEA protein transcripts. Additionally, removal of ABA resulted in rapid attenuation of these oscillatory increases. • Our data demonstrate that dehydration stress-regulated expression of LEA protein genes is temporally dynamic and highlight the importance of oscillations as a robust mechanism for optimal responses. Our results suggest that dehydration stress-induced oscillations in the steady-state abundance of LEA protein transcripts may constitute an important cellular strategy for adaptation to life in a constantly changing environment.
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Affiliation(s)
- Suhas Shinde
- School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland
| | - M Nurul Islam
- School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland
| | - Carl K-Y Ng
- School of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland
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Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro. Biochem Biophys Res Commun 2012; 422:70-4. [PMID: 22560900 DOI: 10.1016/j.bbrc.2012.04.107] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 04/20/2012] [Indexed: 11/22/2022]
Abstract
The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-β (TGF-β). Conversely, migration toward ABA, but not toward TGF-β, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.
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Bruzzone S, Basile G, Mannino E, Sturla L, Magnone M, Grozio A, Salis A, Fresia C, Vigliarolo T, Guida L, De Flora A, Tossi V, Cassia R, Lamattina L, Zocchi E. Autocrine abscisic acid mediates the UV-B-induced inflammatory response in human granulocytes and keratinocytes. J Cell Physiol 2012; 227:2502-10. [PMID: 21898394 DOI: 10.1002/jcp.22987] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
UV-B is an abiotic environmental stress in both plants and animals. Abscisic acid (ABA) is a phytohormone regulating fundamental physiological functions in plants, including response to abiotic stress. We previously demonstrated that ABA is an endogenous stress hormone also in animal cells. Here, we investigated whether autocrine ABA regulates the response to UV-B of human granulocytes and keratinocytes, the cells involved in UV-triggered skin inflammation. The intracellular ABA concentration increased in UV-B-exposed granulocytes and keratinocytes and ABA was released into the supernatant. The UV-B-induced production of NO and of reactive oxygen species (ROS), phagocytosis, and cell migration were strongly inhibited in granulocytes irradiated in the presence of a monoclonal antibody against ABA. Moreover, presence of the same antibody strongly inhibited release of NO, prostaglandin E2 (PGE(2)), and tumor necrosis factor-α (TNF-α) by UV-B irradiated keratinocytes. Lanthionine synthetase C-like protein 2 (LANCL2) is required for the activation of the ABA signaling pathway in human granulocytes. Silencing of LANCL2 in human keratinocytes by siRNA was accompanied by abrogation of the UV-B-triggered release of PGE(2), TNF-α, and NO and ROS production. These results indicate that UV-B irradiation induces ABA release from human granulocytes and keratinocytes and that autocrine ABA stimulates cell functions involved in skin inflammation.
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Affiliation(s)
- Santina Bruzzone
- Department of Experimental Medicine and CEBR, University of Genova, Genova, Italy
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Tao R, Sun HY, Lau CP, Tse HF, Lee HC, Li GR. Cyclic ADP ribose is a novel regulator of intracellular Ca2+ oscillations in human bone marrow mesenchymal stem cells. J Cell Mol Med 2012; 15:2684-96. [PMID: 21251217 PMCID: PMC4373437 DOI: 10.1111/j.1582-4934.2011.01263.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Bone marrow mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine. However, the cellular biology of these cells is not fully understood. The present study characterizes the cyclic ADP-ribose (cADPR)-mediated Ca(2+) signals in human MSCs and finds that externally applied cADPR can increase the frequency of spontaneous intracellular Ca(2+) (Ca(2+) (i) ) oscillations. The increase was abrogated by a specific cADPR antagonist or an inositol trisphosphate receptor (IP3R) inhibitor, but not by ryanodine. In addition, the cADPR-induced increase of Ca(2+) (i) oscillation frequency was prevented by inhibitors of nucleoside transporter or by inhibitors of the transient receptor potential cation melastatin-2 (TRPM2) channel. RT-PCR revealed mRNAs for the nucleoside transporters, concentrative nucleoside transporters 1/2 and equilibrative nucleoside transporters 1/3, IP3R1/2/3 and the TRPM2 channel, but not those for ryanodine receptors and CD38 in human MSCs. Knockdown of the TRPM2 channel by specific short interference RNA abolished the effect of cADPR on the Ca(2+) (i) oscillation frequency, and prevented the stimulation of proliferation by cADPR. Moreover, cADPR remarkably increased phosphorylated extracellular-signal-regulated kinases 1/2 (ERK1/2), but not Akt or p38 mitogen-activated protein kinase (MAPK). However, cADPR had no effect on adipogenesis or osteogenesis in human MSCs. Our results indicate that cADPR is a novel regulator of Ca(2+) (i) oscillations in human MSCs. It permeates the cell membrane through the nucleoside transporters and increases Ca(2+) oscillation via activation of the TRPM2 channel, resulting in enhanced phosphorylation of ERK1/2 and, thereby, stimulation of human MSC proliferation. This study delineates an alternate signalling pathway of cADPR that is distinct from its well-established role of serving as a Ca(2+) messenger for mobilizing the internal Ca(2+) stores. Whether cADPR can be used clinically for stimulating marrow function in patients with marrow disorders remains to be further studied.
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Affiliation(s)
- Rong Tao
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
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Li HH, Hao RL, Wu SS, Guo PC, Chen CJ, Pan LP, Ni H. Occurrence, function and potential medicinal applications of the phytohormone abscisic acid in animals and humans. Biochem Pharmacol 2011; 82:701-12. [DOI: 10.1016/j.bcp.2011.06.042] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2011] [Revised: 06/30/2011] [Accepted: 06/30/2011] [Indexed: 01/22/2023]
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Lee HC. Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. SCIENCE CHINA-LIFE SCIENCES 2011; 54:699-711. [PMID: 21786193 DOI: 10.1007/s11427-011-4197-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Accepted: 06/10/2011] [Indexed: 12/17/2022]
Abstract
The concept advanced by Berridge and colleagues that intracellular Ca(2+)-stores can be mobilized in an agonist-dependent and messenger (IP(3))-mediated manner has put Ca(2+)-mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca(2+)-stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP(3)) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.
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Affiliation(s)
- Hon Cheung Lee
- Department of Physiology, University of Hong Kong, Hong Kong, China.
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Takezawa D, Komatsu K, Sakata Y. ABA in bryophytes: how a universal growth regulator in life became a plant hormone? JOURNAL OF PLANT RESEARCH 2011; 124:437-53. [PMID: 21416316 DOI: 10.1007/s10265-011-0410-5] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2010] [Accepted: 02/11/2011] [Indexed: 05/03/2023]
Abstract
Abscisic acid (ABA) is not a plant-specific compound but one found in organisms across kingdoms from bacteria to animals, suggesting that it is a ubiquitous and versatile substance that can modulate physiological functions of various organisms. Recent studies have shown that plants developed an elegant system for ABA sensing and early signal transduction mechanisms to modulate responses to environmental stresses for survival in terrestrial conditions. ABA-induced increase in stress tolerance has been reported not only in vascular plants but also in non-vascular bryophytes. Since bryophytes are the key group of organisms in the context of plant evolution, clarification of their ABA-dependent processes is important for understanding evolutionary adaptation of land plants. Molecular approaches using Physcomitrella patens have revealed that ABA plays a role in dehydration stress tolerance in mosses, which comprise a major group of bryophytes. Furthermore, we recently reported that signaling machinery for ABA responses is also conserved in liverworts, representing the most basal members of extant land plant lineage. Conservation of the mechanism for ABA sensing and responses in angiosperms and basal land plants suggests that acquisition of this mechanism for stress tolerance in vegetative tissues was one of the critical evolutionary events for adaptation to the land. This review describes the role of ABA in basal land plants as well as non-land plant organisms and further elaborates on recent progress in molecular studies of model bryophytes by comparative and functional genomic approaches.
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Affiliation(s)
- Daisuke Takezawa
- Graduate School of Science and Engineering, Institute for Environmental Science and Technology, Saitama University, Saitama 338-8570, Japan.
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