MODULATION OF THE ANTIOXIDANT DEFENSE AS A FACTOR IN APOPTOSIS

This review focuses on evidence that oxidative stress during apoptosis is controlled, at least in part, by modulating cellular antioxidant d efences. Evidence is presented from studies of apoptosis induced by gl ucocorticoids, HIV-1 infection and tumour necrosis factor-alpha. Gluco corticoid treatment of murine lymphocyte cell lines leads to the down- regulation of primary antioxidant defence enzymes, including catalase, superoxide dismutases, thioredoxin and DT-diaphorase. Following HIV-1 infection, disturbances in glutathione metabolism are seen, and decre ased antioxidant enzyme activities have been reported for HIV-1-infect ed cell lines. The viral protein Tat may mediate these effects. Cellul ar resistance to apoptosis induced by tumour necrosis factor-alpha is modulated by the expression of manganese superoxide dismutase or Bcl-2 . The loss of antioxidant defences is predicted to lead to oxidative s tress, which could contribute to the mechanism of apoptosis through an effect on redox-sensitive transcription factors, calcium homeostasis or cysteine proteases.