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

Abstract

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 (O^-₂) 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 O^-₂ and suppressed that of H₂O₂, suggesting that it inhibits the conversion of O^-₂ 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.