Regulation of reactive oxygen species by nerve growth factor but not Bcl-2 as a novel mechanism of protection of PC12 cells from superoxide anion-induced death.
Although neurotrophins protect PC12 cells and neurons from oxidative stress-induced death, the molecular mechanism of this effect is largely unknown. Xanthine (XA)+xanthine oxidase (XO) increased the production of the superoxide anion (O2-) and hydrogen peroxide (H2O2), and the death of PC12 cells. Catalase but not superoxide dismutase (SOD) nor a NO scavenger protected PC12 cells from death, indicating that H2O2 is the main effector responsible for this cell death. Both nerve growth factor (NGF) and Bcl-2 protected PC12 cells from O2--induced toxicity. NGF enhanced the production of O2- and suppressed that of H2O2, suggesting that it inhibits the conversion of O2- to H2O2, while Bcl-2 had no such effect. These results suggested that NGF protected the cells from oxidative stress by altering the composition of the reactive oxygen species (ROS) without affecting their total level.
Satoh
T
T
Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan.
Yamagata
T
T
Ishikawa
Y
Y
Yamada
M
M
Uchiyama
Y
Y
Hatanaka
H
H
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D018384:Oxidative Stress; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism*
D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013481:Superoxides