EFFECTS OF NERVE GROWTH-FACTOR ON CATALASE AND GLUTATHIONE-PEROXIDASEIN A HYDROGEN PEROXIDE-RESISTANT PHEOCHROMOCYTOMA SUBCLONE

Stepwise selection in increasing H2O2 concentrations was used to obtai n a PC12 cell variant designated HPR. This variant was stably resistan t to H2O2 as compared with the parental PC12 cell line. HPR cells resp onded to nerve growth factor (NGF) by further enhancing H2O2 resistanc e. This variant was subcloned by limiting dilution to obtain the line referred to as HPR-C, which was stably resistant to H2O2 toxicity and retained NGF responses, including morphologic changes and further redu ction of H2O2 toxicity. When compared with the parental PC12 line, the HPR-C subclone did not have higher levels of catalase or glutathione peroxidase (GSH Pr) activity or mRNA expression (as assessed by PCR an alysis of cDNA reverse transcribed from total cellular RNA). HPR-C cel ls retained the ability to respond to NGF treatment by increasing cata lase and GSH Pr activity and expression. These data suggest that the p rotective effects of conditioning lesions, unlike those of neurotrophi ns, are in part independent of changes in the activity or expression o f antioxidant enzymes.