Hydrogen Peroxide-Induced Apoptosis and Necrosis in Human Lung Fibroblasts : Protective Roles of Glutathione

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Although reactive oxygen species (ROS)-related cell damage has been implicated in pathogenesis of fibrogenetic pulmonary disorders, features of ROS-mediated cell death in human lung fibroblasts are not completely understood. We therefore examined the effects of hydrogen peroxide (H2O2) on cell growth kinetics in human lung fibroblasts (HFL-1 cells) and tested the roles of antioxidants on the H2O2-induced cell death (i.e., necrosis and apoptosis) in HFL-1 cells. We found that the relatively low concentrations of H2O2 ranging from 10 μM to 100 μM induced predominantly apoptosis, whereas higher concentration of H2O2 ranging 1 mM - 10 mM induced predominantly necrosis in HFL-1 cells. Extracellular supplementation of glutathione (GSH) in culture media significantly abolished the H2O2-induced cell death, whereas GSH-depleted cells by pretreatment with buthionine sulfoxime (BSO) were likely to undergo cell death caused by a lower concentration of H2O2 than normal HFL-1 cells without BSO treatment. These results indicate that H2O2 induces both necrosis and apoptosis of human lung fibroblasts at least in part through the action of ROS and that modulation of the ROS production inside and outside of cells may influence the cell survival during oxidative insults.
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