GLUTATHIONE-S-TRANSFERASE-8-8 IS LOCALIZED IN SMOOTH-MUSCLE CELLS OF RAT AORTA AND IS INDUCED IN AN EXPERIMENTAL-MODEL OF ATHEROSCLEROSIS
GLUTATHIONE-S-TRANSFERASE-8-8 IS LOCALIZED IN SMOOTH-MUSCLE CELLS OF RAT AORTA AND IS INDUCED IN AN EXPERIMENTAL-MODEL OF ATHEROSCLEROSIS
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DOI：
10.1006/taap.1995.1123
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发表时间：
1995-07-01
影响因子：
3.8
通讯作者：
BOOR, PJ
中科院分区：
文献类型：
--
作者：
MISRA, P;SRIVASTAVA, SK;BOOR, PJ
烯丙胺（AA）是一种亲电子胺，由于其极其有效和相对特异的心血管毒性，具有长期的实验使用历史;它已被用于各种试图模拟人类动脉粥样硬化病变、心肌梗死和血管损伤的实验模型中。尽管AA引起血管病变的确切机制尚未解决，但最近对大鼠AA暴露的急性效应的研究强烈表明，脱氨基作用为醛丙烯醛，氧化应激，以及由此产生的脂质过氧化增加，产生（OH）-O-。自由基和谷胱甘肽（GSH）的急性耗竭可能是AA诱导的血管病变的一些致病因素。鉴于大鼠谷胱甘肽S-转移酶8-8（GST 8 -8）属于GST同工酶的一个独特亚类，参与脂质过氧化产物的解毒作用，我们设计了研究，以探讨AA暴露对大鼠主动脉GST同工酶的影响。这些研究的结果表明，GST 8 -8在大鼠主动脉中表达，并且在AA暴露后显著诱导。通过免疫组织化学，GST 8 -8定位于血管中膜的平滑肌细胞，这被认为是AA代谢的位点。早在AA处理后3天就观察到γ-谷氨酰半胱氨酸合成酶活性和GST对GST 8 -8的优选底物4-羟基壬烯醛和丙烯醛的活性显著增加。GSH和其他GSH相关酶在第3天和第10天的变化支持了这样的概念，即AA阻断后，主动脉防御机制早期响应，GSH生物合成和大鼠GST 8 -8的诱导发生，以减轻丙烯醛的毒性作用，丙烯醛是AA代谢的主要遗传毒性产物。GST 8 -8在不断暴露于脂质过氧化产物的脉管系统中的存在及其由AA诱导，表明GST 8 -8在保护血管免受氧化应激中起关键作用，因此可能参与致动脉粥样硬化过程。(C)出版社：Academic Press
Allylamine (AA) is an electrophilic amine with a long history of experimental usage because of its extremely potent and relatively specific cardiovascular toxicity; it has been utilized in a variety of experimental models attempting to mimic human atherosclerotic lesions, myocardial infarction, and vascular injury. Even though the exact mechanisms by which AA causes vascular lesions remain unresolved, recent studies on the acute effects of AA exposure in rats strongly suggest that deamination to the aldehyde acrolein, oxidative stress, and the resultant increase in lipid peroxidation, generation of (OH)-O-. radicals, and acute depletion of glutathione (GSH) may be some of the causative factors in AA-induced vascular lesions. Since glutathione S-transferase 8-8 (GST8-8) of rat belongs to a distinct subgroup of GST isozymes involved in the detoxification of products of lipid peroxidation, we designed studies to examine the effects of AA exposure on this GST isoform in rat aorta using Western blotting and immunohistochemical techniques. The results of these studies demonstrate that GST8-8 is expressed in rat aorta and is dramatically induced upon AA exposure. By immunohistochemistry, GST8-8 was localized in the smooth muscle cells of the vascular media which is believed to be the site of metabolism of AA. A significant increase in gamma-glutamylcysteine synthetase activity and GST activity toward 4-hydroxynonenal and acrolein, which are preferred substrates of GST8-8, was seen as early as 3 days following AA treatment. Alterations in GSH and other GSH-related enzymes at 3 and 10 days support the concept that-upon AA exposure-aortic defense mechanisms respond early and induction of GSH biosynthesis and rat GST8-8 occur to alleviate the toxic effects of acrolein, a major, genotoxic product of AA metabolism. The presence of GST8-8 in the vasculature, which is constantly exposed to products of lipid peroxidation, and its induction by AA, suggest that GST8-8 plays a key role in protecting blood vessels against oxidative stress and hence, may be involved in the atherogenic process. (C) 1995 Academic Press, Inc.