Role of antioxidant defense mechanisms in protecting gastrointestinal mucosal cclls

在培养的大鼠胃粘膜和内皮细胞的研究中，我们已经证明(1)二乙基二硫代氨基甲酸酯剂量依赖性地增强过氧化氢（H_2O_2）诱导的胃细胞损伤，相应的抑制内源性SOD活性；(2)细胞外谷胱甘肽（GSH）通过促进细胞内谷胱甘肽的合成来保护胃细胞免受h_2o_2的侵害；这是由作用于细胞外谷胱甘肽的γ -谷氨酰转肽酶（为这些细胞提供半胱氨酸）和细胞内γ -谷氨酰半胱氨酸合成酶介导的，这是一种明显不同于肠细胞的谷胱甘肽摄取机制；(3)氧化应激引起胃细胞脂质过氧化，随后发生细胞溶解，铁螯合作用可能通过抑制脂质过氧化作用保护细胞免受氧化应激；(4)谷胱甘肽异丙酯也通过与天然谷胱甘肽类似的摄取机制，通过抑制脂质过氧化来保护胃细胞免受氧化；(5)单氯胺（NH_2Cl）可在幽门螺杆菌感染相关炎症中三途径产生，对胃细胞的毒性大于H_2O_2，细胞内谷胱甘肽对NH_2Cl具有强大的防御作用；(6)乙醇诱导胃细胞产生超氧化物，抑制gsh -氧化还原循环加重乙醇损伤；这种现象在内皮细胞中没有观察到，并且(7)氧化应激诱导胃细胞溶解的机制，由主要研究者假设，本质上与内皮细胞相似。

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.