Aniya Y, Daido A
Laboratory of Physiology and Pharmacology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):123-30. doi: 10.1254/jjp.66.123.
The activation of microsomal glutathione S-transferase in oxidative stress was investigated by perfusing isolated rat liver with 1 mM tert-butyl hydroperoxide (t-BuOOH). When the isolated liver was perfused with t-BuOOH for 7 min and 10 min, microsomal, but not cytosolic, glutathione S-transferase activity was increased 1.3-fold and 1.7-fold, respectively, with a concomitant decrease in glutathione content. A dimer protein of microsomal glutathione S-transferase was also detected in the t-BuOOH-perfused liver. The increased microsomal glutathione S-transferase activity after perfusion with t-BuOOH was reversed by dithiothreitol, and the dimer protein of the transferase was also abolished. When the rats were pretreated with the antioxidant alpha-tocopherol or the iron chelator deferoxamine, the increases in microsomal glutathione S-transferase activity and lipid peroxidation caused by t-BuOOH perfusion of the isolated liver was prevented. Furthermore, the activation of microsomal GSH S-transferase by t-BuOOH in vitro was also inhibited by incubation of microsomes with alpha-tocopherol or deferoxamine. Thus it was confirmed that liver microsomal glutathione S-transferase is activated in the oxidative stress caused by t-BuOOH via thiol oxidation of the enzyme.
通过用1 mM叔丁基过氧化氢（t-BuOOH）灌注分离的大鼠肝脏，研究了氧化应激中微粒体谷胱甘肽S-转移酶的激活情况。当用t-BuOOH灌注分离的肝脏7分钟和10分钟时，微粒体谷胱甘肽S-转移酶活性分别增加了1.3倍和1.7倍，而胞质谷胱甘肽S-转移酶活性未增加，同时谷胱甘肽含量下降。在t-BuOOH灌注的肝脏中还检测到了微粒体谷胱甘肽S-转移酶的二聚体蛋白。用二硫苏糖醇可逆转t-BuOOH灌注后微粒体谷胱甘肽S-转移酶活性的增加，转移酶的二聚体蛋白也消失。当大鼠用抗氧化剂α-生育酚或铁螯合剂去铁胺预处理时，可防止t-BuOOH灌注分离肝脏引起的微粒体谷胱甘肽S-转移酶活性增加和脂质过氧化。此外，在体外，微粒体与α-生育酚或去铁胺孵育也可抑制t-BuOOH对微粒体谷胱甘肽S-转移酶的激活。因此证实，肝脏微粒体谷胱甘肽S-转移酶在t-BuOOH引起的氧化应激中通过酶的硫醇氧化而被激活。
