Role of nitric oxide and peroxynitrite in apoptosis - relation to endonuclease activity

Abstract

Apoptosis is a form of cell death utilized physiologically to maintain tissue homeostasis, as well as in response to various toxic and inflammatory stimuli or anticancer drugs. Since the process of apoptosis is followed by phagocytosis, the cleavage of DNA to low molecular weight material may serve as a protective function limiting the probability of gene transfer to the nuclei of viable neighbor cells. Many different endonucleases have been proposed as candidates responsible for the internucleosomal cleavage of the genomic DNA observed during apoptosis. The main effect was attributed to the alkaline DNase I (Mg 2+ and caspase-dependent) and acid-DNase II. It was also documented that both of them contain a potential protease (caspase) cleavage site, but they can be also activated upon the influence of other "fragmentation factors", including nitric oxide (NO). The complexity of biological effects induced by NO may be the result of the cell redox state changes, due to its potential interaction with superoxide. The apoptotic effect of both, nitric oxide (NO) and peroxynitrite (ONOO) are dose-dependent and cell-specific may point out the existence of possible "inducible" form of endonuclease.