Reactive oxygen species-mediated inactivation of pyruvate dehydrogenase

被引:68
作者
Tabatabaie, T [1 ]
Potts, JD [1 ]
Floyd, RA [1 ]
机构
[1] OKLAHOMA MED RES FDN,FREE RADICAL BIOL & AGING RES PROGRAM,OKLAHOMA CITY,OK 73104
关键词
pyruvate dehydrogenase; ischemia/reperfusion; reactive oxygen species; superoxide radical; hydroxyl radical;
D O I
10.1006/abbi.1996.0560
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Brain ischemia reperfusion causes increased formation of reactive oxygen species (ROS). Activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) has been shown to undergo a significant decrease following reperfusion of the ischemic tissue. We have examined the effect of a superoxide radical-generating system (xanthine oxidase/hypoxanthine, XO/HX) on the activity of this enzyme. Incubation of PDH in the presence of XO/HX resulted in its inactivation. The degree of the inactivation was dependent on the amount of XO present, which correlated linearly with the concentration of superoxide radical generated by this system. The activity of lactate dehydrogenase, an enzyme resistant to inactivation by ischemia reperfusion, was not affected by this system. Superoxide dismutase partially prevented and catalase exerted a nearly complete protective effect against the inactivation of PDH. Deferoxamine was partially protective, The sulfhydryl protective reagents, dithiothreitol and glutathione, prevented the inactivation of PDH, even though to varying-degrees, which implicates sulfhydryl oxidation. A hydroxyl radical-generating system (hydrogen peroxide irradiated with ultraviolet radiation) effectively inactivated PDH. These results demonstrate that PDH is susceptible to damage and inactivation by ROS and point to the involvement of Fenton chemistry and hydroxyl radicals formed through it in PDH inactivation by XO/HX, A similar mechanism may be responsible for the PDH inactivation during ischemia/reperfusion. (C) 1996 Academic Press, Inc.
引用
收藏
页码:290 / 296
页数:7
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