Shinji Teramoto, Tetsuji Tomita, Hirotoshi Matsui, Eijiro Ohga, Takeshi
Matsuse and Yasuyoshi Ouchi
Department of Geriatric Medicine, Tokyo University Hospital, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-8655, Japan
Abstract: 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 microM
to 100 microM 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.
Keywords: Hydrogen peroxide, Apoptosis, Necrosis, Antioxidant, Lung fibroblast