Effects of nerve growth factor on catalase and glutathione peroxidase in a hydrogen peroxide-resistant pheochromocytoma subclone

Stepwise selection in increasing H₂O₂ concentrations was used to obtain a PC12 cell variant designated HPR. This variant was stably resistant to H₂O₂ as compared with the parental PC12 cell line. HPR cells responded to nerve factor (NGF) by further enhancing H₂O₂ resistance. 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 reduction 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 Px) activity or mRNA expression (as assessed by PCR analysis of cDNA reverse transcribed from total cellular RNA). HPR-C cells retained the ability to respond to NGF treatment by increasing catalase and GSH Px activity and expression. These data suggest that the protective effects of conditioning lesions, unlike those of neurotrophins, are in part independent of changes in the activity or expression of antioxidant enzymes.