Potential role of NADPH oxidase in pathogenesis of pancreatitis

Figure 1 Potential mechanism of nicotinamide adenine dinucleotide phosphate oxidase activation via cholecystokinin receptor. Cerulein and cholecystokinin (CCK) receptor binding triggers transient Ca²⁺ release from the endoplasmic reticulum to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is mediated by PLC and IP3. Reactive oxygen species (ROS) generated by NADPH oxidase activate IκB kinase to phosphorylate IκB in the cytosol. Phosphorylated IκB is ubiquitinated and degraded in a proteasome-dependent manner. NF-κB translocates to the nucleus and regulates expression of cytokines to participate in the pathogenesis of pancreatitis.

Figure 2 Activation and inhibition factors of nicotinamide adenine dinucleotide phosphate oxidase signal transduction in the pathogenesis of pancreatitis. Cerulein, Ang II and platelet derived growth factor (PDGF) can enhance, while VIP can decrease the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Ethanol can augment the activation of the cell’s NADPH oxidase system stimulated by PDGF. The downstream signal molecules including MAPKs, TPK, NF-κB, JAK/STAT and Akt participate in the pathogenesis of pancreatitis. TNF: Tumor necrosis factor; IL: Interleukin; TPK: Tyrosine protein kinase; MAPK: Mitogen activated protein kinase.