Role of α class glutathione S-transferases as antioxidant enzymes in rodent tissues

被引:66
|
作者
Yang, YS
Sharma, R
Zimniak, P
Awasthi, YC
机构
[1] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA
[2] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA
[4] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA
关键词
glutathione S-transferases; glutathione peroxidase; lipid peroxidation; phospholipid hydroperxides;
D O I
10.1006/taap.2002.9450
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Glutathione S-transferases (GST) are multifunctional proteins. a class GSTs are known to catalyze glutathione peroxidase reactions, in addition to their major activity, i.e., conjugation of electrophiles to glutathione. In the present work, the contribution of rat and mouse a class GSTs to glutathione-dependent reduction of phospholipid hydroperoxides has been studied., Results of these studies indicate that the a class GST fraction, which consists of three isoforms, has glutathione peroxidase activity toward phospholipid hydroperoxides residing in biological membranes, without the need of prior phospholipase C action. Immunotitration studies using antibodies specific to the a class GSTs, GSTA1-1, GSTA2-2, and GSTA3-3, indicate that these GST isozymes account for approximately half of the glutathione peroxidase activity toward phospholipid hydroperoxides present in the 28,000g supernatant fractions of rat and mouse liver extracts. GSTs contribute proportionally lesser fraction of this activity in other tissues in which a class GSTs are less prevalent. In mice, the contribution of a class GSTs to the overall glutathione peroxidase activity is indistinguishable in wild-type mice and knockout mice lacking the major selenoenzyme, glutathione peroxidase 1, an enzyme that does not act on intact phospholipid hydroperoxides. These results are consistent with our previous studies on human a class GSTs (Yang, et al. J. Biol. Chem. 276, 19220-19230, 2001) and demonstrate that a class GSTs are of physiological importance, not only in the conjugative detoxification of electrophiles, but are also an essential component of cellular antioxidant defense mechanisms. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:105 / 115
页数:11
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