Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. II. A conditioning lesion paradigm.

The PC12 rat pheochromocytoma cell line is a nerve growth factor (NGF) responsive line that is protected by NGF from the toxic effects of hydrogen peroxide induced peroxidation. In part, NGF protection of PC12 cells acts through a shift in oxidant-antioxidant metabolism by the enhancement of catalase activity. When PC12 cells are used in a conditioning lesion paradigm to study the effects of an initial sublethal peroxidative insult on subsequent responses to injury, a low dose conditioning lesion protects even in the absence of NGF. The magnitude of the protective effect exerted by the conditioning lesion, however, is augmented in the presence of NGF, since a significant cytoprotective effect is observed over a wider range of H2O2 concentrations. Neuronal injury due to treatment with a high dose of H2O2 (5 mM) has a cytotoxic effect that cannot be prevented by NGF treatment and is, in itself, not conditioning in nature. This in vitro model system lends itself to the development of explanations regarding the salutory effects of conditioning lesions at the molecular level.