Inhibition of poly (ADP-ribose) synthetase (PARS) and protection against peroxynitrite-induced cytotoxicity by zinc chelation

摘要

1. Peroxynitrite, a potent oxidant formed by thereaction of nitric oxide and superoxide causes thymocyte necrosis, in part, via activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). The cytotoxic PARS pathway initiated by Dna strand breaks and excessive PARS activation has been shown to deplete cellularenergy pools, leading to cell necrosis, Here we have investigated the effect of tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) a heavy metal chelator on peroxynitrite-induced cytotoxicity.