INTERLEUKIN 1-INDUCED PRODUCTION OF NITRIC-OXIDE INHIBITS BENZENTRIOL-MEDIATED OXIDATIVE INJURY IN RAT HEPATOCYTES
INTERLEUKIN 1-INDUCED PRODUCTION OF NITRIC-OXIDE INHIBITS BENZENTRIOL-MEDIATED OXIDATIVE INJURY IN RAT HEPATOCYTES
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DOI：
10.1016/0016-5085(95)90286-4
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发表时间：
1995-07-01
期刊：
影响因子：
29.4
通讯作者：
ABE, KY
中科院分区：
文献类型：
--
作者：
KUO, PC;ABE, KY
背景与目的：一氧化氮在体内和体外多种系统中调节自由基介导的细胞过程。本研究的目的是确定肝细胞产生NO在氧化损伤中的作用。方法：原代培养的大鼠肝细胞与超氧物来源1，2，3-苯三酚共同孵育。加入白细胞介素1(IL 1)诱导NO合成。用天冬氨酸氨基转移酶(AST)、丙二醛(MDA)和谷胱甘肽(GSH)测定损伤程度。结果：苯三醇诱导的损伤使对照组和IL-1处理组的AST和MDA水平升高，GSH水平降低。抑制IL-1处理的细胞中的NO合成显著增加AST和MDA的产生，同时促进GSH的消耗。在超氧化物歧化酶或外源性NO来源S亚硝酸白蛋白的存在下，损伤减轻或消除。NO的产生随着氧化应激的增加而显著增加。在苯三醇诱导的IL-1刺激的肝细胞损伤中，逆转录聚合酶链式反应显示诱导型一氧化氮合酶信使RNA水平显著增加，而免疫印迹分析显示诱导型一氧化氮合酶蛋白水平同样增加。结论：在IL-1/苯三醇介导的大鼠肝细胞损伤模型中，来自内源性合成或外源性供体的NO具有保护作用。氧化应激可能在NO合成的转录调控中起作用。
Background & Aims: Nitric oxide modifies free radical-mediated cell processes in multiple in vivo and in vitro systems. The aim of this study was to determine the role of hepatocyte production of NO in oxidative injury. Methods: Rat hepatocytes in primary culture were incubated with 1,2,3-benzenetriol, a source of superoxide. Interleukin (IL) 1 was added to induce NO synthesis. injury was determined by aspartate aminotransferase (AST), malondialdehyde (MDA), and glutathione (GSH) levels. Results: Benzenetriol-induced injury increased AST and MDA levels and decreased GSH levels in control and IL-1-treated cells. Inhibition of NO synthesis in IL-1-treated cells significantly increased AST and MDA production while enhancing GSH depletion. In the presence of superoxide dismutase or S-nitroso-albumin, an exogenous source of NO, injury was decreased or abolished. NO production was significantly increased with oxidative stress. In benzenetriol-induced injury in IL-1-stimulated hepatocytes, reverse-transcription polymerase chain reaction showed significantly increased levels of inducible NO synthase messenger RNA, whereas immunoblot analysis showed similarly increased levels of inducible NO synthase protein. Conclusions: In this rat hepatocyte model of IL-1/benzenetriol-mediated injury, NO, derived from endogenous synthesis or an exogenous donor, is protective. Oxidative stress may have a role in the transcriptional control of NO synthesis.