Hepatocyte growth factor modulates H2O2-induced mesangial cell apoptosis through induction of heme oxygenase-1.
Oxidative stress plays an important role in the induction of mesangial cell (MC) injury. In the present study, we evaluated the molecular mechanism involved in hydrogen peroxide (H2O2)-induced MC apoptosis. In addition, we examined the role of heme oxygenase-1 (HO-1) in hepatocyte growth factor (HGF)-modulated, H2O2-induced MC injury. H2O2 promoted (p < 0.001) mouse MC (MMC) apoptosis. This effect of H2O2 was associated with translocation of cytochrome c from the mitochondrial to the cytosolic compartment. In addition, a caspase-9 inhibitor partially attenuated this effect of H2O2. These findings suggest that H2O2-induced MMC apoptosis is mediated through the mitochondrial pathway. HGF not only prevented H2O2-induced MMC apoptosis, but also inhibited H2O2-induced translocation of cytochrome c from the mitochondrial to the cytosolic compartment. HGF also promoted the expression of HO-1 by MMCs; interestingly, hemin inhibited (p < 0.001) H2O2-induced MMC apoptosis. On the other hand, zinc protoporphyrin inhibited the protective influence of HGF on H2O2-induced MMC apoptosis. These findings suggest that H2O2-induced apoptosis occurs through the mitochondrial pathway. HGF provides protection against H2O2-induced MMC apoptosis through induction of HO-1.
Radhakrishnan
Neetu
N
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11042, USA.
Bhaskaran
Madhu
M
Singhal
Pravin C
PC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology* / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
D016877:Oxidants; D017228:Hepatocyte Growth Factor; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases