NADP-异柠檬酸脱氢酶对百草枯介导的心脏线粒体 aconitase 氧化失活的保护作用。

Protective effect of NADP-isocitrate dehydrogenase on the paraquat-mediated oxidative inactivation of aconitase in heart mitochondria.

机构信息

Department of Biochemistry, Aichi Medical University, School of Medicine, Nagakute, Aichi 480-1195, Japan.

出版信息

Environ Toxicol Pharmacol. 2006 Sep;22(2):148-52. doi: 10.1016/j.etap.2006.02.001. Epub 2006 Mar 6.

DOI:10.1016/j.etap.2006.02.001

Abstract

Protective role of NADP-isocitrate dehydrogenase in the oxidative inactivation of mitochondrial enzymes was analyzed. Administration of paraquat to the rat inactivated liver mitochondrial enzymes: the aconitase activity decreased to one quarter, and citrate synthase and fumarase to half, whereas cytosolic enzymes were not affected. Activities of heart mitochondrial and cytosolic enzymes were not at all changed in the rat treated with paraquat, but paraquat directly inactivated aconitase in the heart mitochondria isolated from the non-treated rats. The paraquat-dependent inactivation of aconitase was prevented by activating NADP-isocitrate dehydrogenase in the presence of oxidized glutathione. NADP-isocitrate dehydrogenase could regenerate glutathione in isolated heart mitochondria, indicating that paraquat-mediated inactivation depends on the glutathione-regenerating activity by enhanced NADPH supply. Lower NADP-isocitrate dehydrogenase activity in liver mitochondria cannot regenerate reduced glutathione for scavenging reactive oxygen species, resulting in the paraquat-induced oxidative inactivation of mitochondrial enzymes. However, higher activity of NADP-isocitrate dehydrogenase participates in the regeneration of reduced glutathione causing stabilization of enzymes in heart mitochondria.

摘要

分析了 NADP-异柠檬酸脱氢酶在保护线粒体酶免受氧化失活中的作用。给大鼠注射百草枯会使肝线粒体酶失活：乌头酸酶活性降至四分之一，柠檬酸合酶和延胡索酸酶活性降至一半，而胞质酶不受影响。百草枯处理的大鼠心脏线粒体和胞质酶的活性均未发生变化，但百草枯可直接使未经处理的大鼠心脏线粒体中的乌头酸酶失活。在氧化型谷胱甘肽存在下激活 NADP-异柠檬酸脱氢酶可防止乌头酸酶的百草枯依赖性失活。NADP-异柠檬酸脱氢酶可在分离的心脏线粒体中再生谷胱甘肽，表明百草枯介导的失活依赖于增强 NADPH 供应的谷胱甘肽再生活性。肝线粒体中 NADP-异柠檬酸脱氢酶活性较低，无法再生用于清除活性氧的还原型谷胱甘肽，导致线粒体酶发生百草枯诱导的氧化失活。然而，较高活性的 NADP-异柠檬酸脱氢酶参与还原型谷胱甘肽的再生，导致心脏线粒体中酶的稳定。