Hepatocyte growth factor improves viability after H2O2-induced toxicity in bile duct epithelial cells

作者：Arends Brigitte^*; Slump Estel; Spee Bart; Rothuizen Jan; Penning Louis C

来源：Comparative Biochemistry and Physiology C-Toxicology & Pharmacology, 2008, 147(3): 324-330.

DOI：10.1016/j.cbpc.2007.12.001

• caspase-3
• cholangiocyte
• glutathione
• HGF
• H2O2
• oxidative stress
• ROS

Intracellular defence mechanisms against oxidative stress may play an important role in the progression of liver diseases, including cholangiopathies. The multifunctional anti-apoptotic hepatocyte growth factor (HGF) has been suggested to have antioxidant functions. The effect of HGF upon cell viability, the generation of ROS, the expression of genes that play a role in ROS defence, and the activation of caspase-3 were measured in bile duct epithelial (BDE) cells in the presence or absence of H2O2. HGF reduced H2O2-induced loss of viability, diminished H(2)O(2)mediated ROS generation and abrogated H2O2-triggered changes in GSH/GSSG ratio. Furthermore, HGF increased the gene-expression of gamma-glutamylcysteine synthetase (GCLC) and glutathione reductase (GSR), while no effect was seen upon the gene-expression of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase (GPX1), and glutathione synthetase (GSR). Finally, HGF diminished the proteolytical activation of the key mediator of apoptosis (caspase-3) after H2O2 exposure. Together, HGF may improve viability in bile duct epithelia cells after H2O2 induced toxicity by proliferation, strengthening the intrinsic antioxidant defences, and/or by an attenuation of apoptosis. These in vitro results support the evaluation of HGF as antioxidative factor in hepatobiliary pathologies.

• 出版日期2008-4