Inflammatory Cytokines Induce Oxidative Stress And Apoptosis In PC12 Cells

Abstract

Inflammation causes oxidative stress, which plays a critical role in neurodegenerative diseases such as multiple sclerosis and diabetic neuropathy. We have shown that PC12 cells exposed to metals such as manganese and cobalt (which causes oxidative stress) underwent apoptotic cell death. Treatment with reducing agents such as glutathione reversed the effect, suggesting oxidative stress processes were involved. Caspase activity was induced, indicating that cell death was apoptotic. It is known that inflammation contributes to progression of the disease. We investigated whether inflammatory cytokines contribute to cell death by activating oxidative pathways. PC12 cells treated with interferon gamma showed 60% loss in viability. Inhibitors of caspase‐3, −8 and −9 activity prevented cell death. Inducible nitric oxide synthase gene transcription was upregulated within 6 hours of treatment with IFN gamma as well as TNF/LPS treatment. Increase in the level for nitrite was observed using Griess reagent. and might be selectively exposed to iNOS‐mediated oxidative damage as a consequence of elevated TNFα levels. Our results suggest that oxidative stress induces cell death involving iNOS and caspase induction.