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Role of antioxidant defense mechanisms in protecting gastrointestinal mucosal cclls

抗氧化防御机制在保护胃肠粘膜细胞中的作用

基本信息

批准号：
06670581
负责人：
HIRAISHI Hideyuki
金额：
$ 1.15万
依托单位：
Dokkyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670581/
关键词：
Reactive oxygen species Superoxide dismutase Glutathione Lipid peroxidation Cytolysis Iron Monochloramine 過酸化脂質

项目摘要

In studies with the use of cultured rat gastric mucosal and endothelial cells, we have demonstrated that (1) diethyldithiocarbamate dose-dependently enhanced hydrogen peroxide (H_2O_2) -induced damage to gastric cells, corresponding with inhibition of endogenoud SOD activity ; (2) extracellular glutahione (GSH) potects gastric cells from H_2O_2by accelerating intracellular GSH synthesis ; this is mediated by gamma-glutamyl transpcptidase acting on extracellular GSH (which supplies these cells with cysteine) and then by intracellular gamma-glutamylcysteine synthelase, a mechanism of GSH uptake distinctly different from that of intestinal cells ; (3) oxidant stress causes lipid peroxidation of gastric cells, which is then followed by cytolysis, and iron chelation protccls cells from oxidant stress presumably through inhibition of lipid peroxidation ; (4) GSH isopropylester also protccts gastric cclls from oxidant throuhg inihibition of lipid peroxidation, by an uptake mechanism similar to that of native GSH ; (5) monochloramine (NH_2Cl), which could be threoretically produced in Helicobacter pylori infection-associated inflammation, is more toxic to gastric cells than H_2O_2, and intracellular GSH plays a role as a potent defense system against NH_2Cl ; and (6) ethanol induces superoxide generation by gastric cells, and inhibition of the GSH-redox cycle aggravates ethanol damage ; such phenomena cannot be observed in endothelial cells, and (7) the mechanisms by which oxidant stress induces cytolysis of gastric cells, postulated by the prineipal investigator, is essentially similar to those of endothelial cells.

用培养的大鼠胃粘膜细胞和内皮细胞研究表明：（1）二乙基二硫代氨基甲酸盐（DTG）剂量依赖性地增强过氧化氢（H_2O_2）对胃粘膜细胞的损伤，相应地抑制内源性SOD活性：（2）细胞外谷胱甘肽（GSH）通过促进细胞内GSH的合成而保护胃粘膜细胞免受H_2O_2的损伤;这是由作用于细胞外GSH的γ-谷氨酰转肽酶介导的（其向这些细胞提供半胱氨酸），然后通过细胞内γ-谷氨酰半胱氨酸脱氢酶，这是一种与肠细胞明显不同的GSH摄取机制;（3）氧化应激引起胃粘膜细胞脂质过氧化，脂质过氧化导致细胞溶解，铁螯合物可能通过抑制脂质过氧化保护胃粘膜细胞免受氧化应激;（4）GSH异丙酯对胃粘膜细胞也有保护作用，其作用机制与天然GSH相似：（5）H_2O_2对胃粘膜细胞的毒性比H_2Cl更强，而H_2Cl可在幽门螺杆菌感染相关的炎症反应中产生，细胞内GSH可作为一种有效的抗NH_2Cl系统;（6）乙醇诱导胃细胞产生超氧化物，GSH-氧化还原循环的抑制加剧乙醇损伤;这种现象在内皮细胞中不能观察到，（7）由主要研究者假设的氧化应激诱导胃细胞溶解的机制基本上与内皮细胞的机制相似。