Role of poly(ADP-ribose) synthetase activation in the suppression of cellular energetics in response to nitric oxide and peroxynitrite.

Poly(ADP-ribose) synthetase (PARS) activation: a pathway of cellular oxidant injury PARS is a protein-modifying and nucleotidepolymerizing enzyme that is abundantly present in the nucleus [l]. Its activation results in the cleavage of NAD' into ADP-ribose and nicotinamide. In turn, PARS covalently attaches ADPribose to various proteins, including nuclear proteins, histones and an automodification domain of PARS itself. PARS then extends the initial ADP-ribose group into a nucleic acid-like polymer, poly(ADP-ribose) [ 11. The physiological function of PARS has been the subject of debate. Initial work has implicated it in the process of DNA repair [ l ] . However, according to more recent data, it is not efficient as a DNA-repair enzyme [2]. On the contrary, it has been suggested that the physiological role of PARS is to slow cellular metabolism as an adaptive response to altered environmental conditions [3-51. In addition, there is also some evidence that PARS plays a role in the regulation of gene expression and cell differentiation, by regulating histone reshuffling