Brain-derived neurotrophic factor prevents superoxide anion-induced death of PC12h cells stably expressing TrkB receptor via modulation of reactive oxygen species

In our previous report (Satoh et al., 1999. Regulation of reactive oxygen s pecies by nerve growth factor but not by Bcl-2 as a novel mecahnism of prot ection of PC12 cells from superoxide anion-induced death. J. Biochem. 125, 952-959), we reported that nerve growth factor (NGF) protected PC12 cells f rom superoxide anion (O-2(-))-induced cell death through a novel regulation of reactive oxygen species (ROS) which increased O-2(-) and decreased hydr ogen peroxide (H2O2), indicating that decreasing conversion from O-2(-) to H2O2 is a critical process for the protection by NGF. In the present study, we performed a comparative study on protective mechanisms between NGF and brain-derived neurotrophic factor (BDNF) using TrkB-expressing PC12h cells. When compared with NGF, BDNF induced a weaker but significant protective e ffect on the cells from O(2)(-)induced death. BDNF did not seem to change t he total amount of ROS in the cells treated with xanthine and xanthine oxid ase. On the other hand, BDNF increased O-2(-) and decreased H2O2 levels in the same cells, although not so strongly as NGF. These results suggest that decreasing conversion from O-2(-) to H2O2 is also critical for the protect ion by BDNF, which is considered to play a central role in survival and dif ferentiation of CNS neurons. (C) 1999 Elsevier Science Ireland Ltd. All rig hts reserved.