Glutathione S-transferases in human and rodent skin: multiple forms and species-specific expression.
Glutathione S-transferases in human and rodent skin: multiple forms and species-specific expression.
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人类和啮齿动物皮肤中的谷胱甘肽 S-转移酶：多种形式和物种特异性表达。
DOI：
10.1111/1523-1747.ep12470150
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Mukhtar,H
中科院分区：
文献类型：
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作者：
Raza,H;Awasthi,YC;Zaim,MT;Eckert,RL;Mukhtar,H
谷胱甘肽S-转移酶（GST）是一类广泛分布的多功能解毒酶家族，催化还原型谷胱甘肽与多种亲电试剂之间的反应。令人感兴趣的是，几种皮外组织表现出不同的同工酶谱，这些同工酶以高度受控的方式表达。尽管事实上，皮肤是不断暴露于许多有害的代理商，很少有人知道GST同工酶的表达和它们的作用，在皮肤组织中的生理和外源性底物的代谢。使用特定的多克隆抗体的α，Mu和Pi类GST，我们确定了它们在大鼠，小鼠和人类皮肤细胞质中的表达。在每个物种中，GST同工酶对1-氯-2，4-二硝基苯，苯并（a）芘4，5-氧化物，苯乙烯7，8-氧化物，白三烯A4，和ethacrynic酸的活性，但不对溴磺酞和氢过氧化枯烯。蛋白质印迹分析表明，Pi同工酶在所有三个物种的优势表达。α类同工酶仅存在于人皮肤中，而Mu类同工酶仅在大鼠和小鼠皮肤中检测到。同样，在正常和转化培养的人角质形成细胞Pi的主要同工酶。使用免疫组织化学技术的原位定位研究证实了Western印迹法的观察结果。在小鼠皮肤中，发现Pi和Mu同工酶主要位于皮脂腺中，而没有观察到与α类同工酶的反应性。我们的数据表明，多种形式的GST存在于啮齿动物和人类皮肤和GST Pi是在每个物种的主要同工酶。此外，皮肤GST可以代谢内源性底物和外源性化合物。
The glutathione S-transferases (GST) are a family of widely distributed multifunctional detoxification enzymes that catalyze the reaction between reduced glutathione and a variety of electrophiles. Of interest is the fact that several extracutaneous tissues exhibit a distinct spectrum of isozymes that are expressed in a highly controlled fashion. Despite the fact that the skin is continuously exposed to numerous injurious agents, little is known about the expression of GST isozymes and their role in metabolism of physiologic and xenobiotic substrates in cutaneous tissue. Using specific polyclonal antibodies to the Alpha, Mu, and Pi classes of GST, we identified their expression in rat, mouse, and human skin cytosol. In each species, GST isozymes expressed activities towards 1- chloro-2,4-dinitrobenzene, benzo(a)pyrene 4,5-oxide, styrene 7,8-oxide, leukotriene A4, and ethacrynic acid, but not towards bromosulfophthalein and cumene hydroperoxide. Western blot analysis indicated the predominant expression of Pi isozyme in all three species. Alpha class of isozyme(s) was present only in human skin, whereas Mu class of isozyme(s) was detected only in rat and mouse skin. Similarly, in normal and transformed cultured human keratinocytes Pi was the predominant isozyme. In situ localization studies using immunohistochemical techniques confirmed the observations of Western blotting. In mouse skin, Pi and Mu isozyme(s) were found to be predominantly localized in sebaceous glands, whereas no reactivity was observed with the Alpha class of isozymes. Our data show that multiple forms of GST exist in rodent and human skin and that GST Pi is the predominant isozyme in each species. Furthermore, cutaneous GST can metabolize both endogenous substrates and foreign compounds.