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World J Gastroenterol. Jan 7, 2008; 14(1): 76-80
Published online Jan 7, 2008. doi: 10.3748/wjg.14.76
Midkine secretion protects Hep3B cells from cadmium induced cellular damage
Nuray Yazihan, Haluk Ataoglu, Ethem Akcil, Burcu Yener, Bulent Salman, Cengiz Aydin
Nuray Yazihan, Haluk Ataoglu, Burcu Yener, Molecular Biology Research and Development Unite, Faculty of Medicine, Ankara University, Ankara 06500, Turkey
Nuray Yazihan, Ethem Akcil, Pathophysiology Department, Ankara University, Faculty of Medicine, Ankara 06500, Turkey
Haluk Ataoglu, Microbiology Department, Ankara University, Faculty of Medicine, Ankara 06500, Turkey
Bulent Salman, General Surgery Department, Faculty of Medicine, Gazi University, Ankara 06500, Turkey
Cengiz Aydin, Clinical Biochemistry Laboratory, Dogubeyazit Dr. Yasar Eryilmaz Government Hospital, Agri, Turkey
Correspondence to: Nuray Yazihan, MD, PhD, Molecular Biology Research and Development Unite, Faculty of Medicine, Ankara University, Morfoloji Binasi, Sihhiye, Ankara 06100,Turkey. nurayyazihan@yahoo.com
Telephone: +90-312-3103010-372
Fax: +90-312-3106370
Received: August 3, 2007
Revised: September 16, 2007
Published online: January 7, 2008
Abstract

AIM: To evaluate role of midkine secretion during Cadmium (Cd) exposure in the human hepatocyte cell line Hep3B cells.

METHODS: Different dosages of Cd (0.5-1-5-10 &mgr;g/mL) were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase (LDH) leakage and midkine secretion were evaluated as time dependent manner. Same experiments were repeated with exogenously applied midkine (250-5000 pg/mL) and/or 5 &mgr;g/mL Cd.

RESULTS: Cd exposure induced prominent apoptosis and LDH leakage beginning from lower dosages at the 48th h. Cd induced midkine secretion with higher dosages (P < 0.001), (control, Cd 0.5-1-5-10 &mgr;g/mL respectively: 1123 ± 73, 1157 ± 63, 1242 ± 90, 1886 ± 175, 1712 ± 166 pg/mL). Exogenous 500-5000 pg/mL midkine application during 5 &mgr;g/mL Cd toxicity prevented caspase-3 activation (control, Cd toxicity, 250, 500, 1000, 2500, 5000 pg/mL midkine+ Cd toxicity, respectively: 374 ± 64, 1786 ± 156, 1545 ± 179, 1203 ± 113, 974 ± 116, 646 ± 56, 556 ± 63 cfu) LDH leakage and cell death in Hep3B cells (P < 0.001).

CONCLUSION: Our results showed that midkine secretion from Hep3B cells during Cd exposure protects liver cells from Cd induced cellular damage. Midkine has anti-apoptotic and cytoprotective role during Cd toxicity. Further studies are needed to explain the mechanism of midkine secretion and cytoprotective role of midkine during Cd exposure. Midkine may be a promising therapeutic agent in different toxic hepatic diseases.

Keywords: Cadmium; Midkine; Hepatocyte; Apoptosis; Caspase-3; Lactate dehydrogenase