Szabó C, Dawson V L
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Trends Pharmacol Sci. 1998 Jul;19(7):287-98. doi: 10.1016/s0165-6147(98)01193-6.
Oxidative and nitrosative stress can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). This enzyme has also been termed poly(ADP-ribose) polymerase (PARP) or poly(ADP-ribose) transferase (pADPRT). Rapid activation of the enzyme depletes the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. In this article, Csaba Szabó and Valina Dawson overview the impact of pharmacological inhibition or genetic inactivation of PARS on the course of oxidant-induced cell death in vitro, and in inflammation and reperfusion injury in vivo. A major trigger for DNA damage in pathophysiological conditions is peroxynitrite, a cytotoxic oxidant formed by the reaction between the free radicals nitric oxide and superoxide. The pharmacological inhibition of poly(ADP-ribose) synthetase is a novel approach for the experimental therapy of various forms of inflammation and shock, stroke, myocardial and intestinal ischaemia-reperfusion, and diabetes mellitus.
氧化应激和亚硝化应激可引发DNA链断裂，进而激活核酶聚（ADP - 核糖）合成酶（PARS）。该酶也被称为聚（ADP - 核糖）聚合酶（PARP）或聚（ADP - 核糖）转移酶（pADPRT）。该酶的快速激活会耗尽其底物烟酰胺腺嘌呤二核苷酸的细胞内浓度，从而减缓糖酵解、电子传递以及随后的ATP生成速率。这一过程可导致细胞功能障碍和细胞死亡。在本文中，恰巴·绍博和瓦利纳·道森概述了PARS的药理学抑制或基因失活对体外氧化应激诱导的细胞死亡过程以及体内炎症和再灌注损伤的影响。病理生理条件下DNA损伤的一个主要触发因素是过氧亚硝酸盐，它是由自由基一氧化氮和超氧化物反应形成的一种细胞毒性氧化剂。聚（ADP - 核糖）合成酶的药理学抑制是用于各种形式炎症和休克、中风、心肌和肠道缺血再灌注以及糖尿病实验治疗的一种新方法。
