Antioxidant Enzymes and Apoptosis

The role of antioxidant enzymes can be interpreted in terms of fine tuning of the concentration of reactive oxygen species which are required in the redox regulation of the cell cycle and of programmed cell death. This review summarizes findings from papers published in the last few years which deal with the relation between apoptosis and the two antioxidant enzymes, manganous superoxide dismutase (MnSOD) and catalase. With respect to MnSOD, the literature is much in favor of an inhibitory action in apoptosis. Increased MnSOD activity has been shown to prevent cell death via the receptor-mediated apoptotic pathway as well as cell death via the mitochondrial pathway. The literature on the influence of catalase activity on apoptosis is less consistent. Evidence for both an antiapoptotic and a proapoptotic role of catalase can be found. From the results reviewed here, two schemes for the involvement of MnSOD and catalase in the regulation of apoptosis can be extracted: 1) Both MnSOD and catalase inhibit apoptosis by removing superoxide anion radicals or H2O2, respectively, because these reactive oxygen species are mediators required for the apoptotic program or inhibit a survival pathway. 2) An increase in H2O2 by downregulation or inhibition of catalase activity and or downregulation of MnSOD activity inhibits apoptosis while a decrease in H2O2 by upregulation of catalase activity and or upregulation of MnSOD activity supports apoptosis, possibly because of a supportive role of H2O2 in a survival pathway. The data reported so far do not allow for an explanation why some cell models appear to fit the first scheme while the second scheme appears to correctly describe other cell models. The present state of the literature reveals that antioxidant enzymes play a more intricate role in cell physiology than previously assumed.