Species variations in cutaneous alcohol dehydrogenases and aldehyde dehydrogenases may impact on toxicological assessments of alcohols and aldehydes
Species variations in cutaneous alcohol dehydrogenases and aldehyde dehydrogenases may impact on toxicological assessments of alcohols and aldehydes
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DOI：
10.1016/s0300-483x(02)00552-8
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发表时间：
2003-03-03
期刊：
影响因子：
4.5
通讯作者：
Pease, CKS
中科院分区：
文献类型：
--
作者：
Cheung, C;Davies, NG;Pease, CKS
乙醇脱氢酶(ADH；EC.1.1.1)和乙醛脱氢酶(ALDH；EC 1.2.1.3)在内源和外源醇醛代谢中都起着重要作用。用免疫印迹分析和免疫组织化学方法研究了ADH(1-3)和ALDH(1-3)在小鼠(BALB/c和Cba/ca)、大鼠(17344)和豚鼠(Dunkin-Hartley)皮肤和肝脏中的表达和定位。在人类皮肤中也检测到了ALDH2的表达和定位，而在小鼠、豚鼠和人皮肤胞浆中则研究了ADH催化的乙醇氧化。Western印迹分析表明，ADH-1、ADH-3、ALDH-I和ALDH2在小鼠、大鼠和豚鼠的皮肤和肝脏中分别表达。ADH2在任何啮齿动物物种/品系的皮肤中都没有检测到，但在所有啮齿动物的肝脏中都存在。ALDH3在两个品系的小鼠和大鼠的皮肤中都有表达，但在豚鼠皮肤中没有检测到，在所有肝脏中都没有检测到。免疫组织化学显示ADH和ALDH在小鼠、大鼠、豚鼠和人皮肤切片中的表达模式相似，主要定位于表皮、皮脂腺和毛囊。ADH活性(表观V-max，nmoles/mg蛋白/min)在肝脏(6.02-16.67)高于皮肤(0.32-1.21)，在人皮肤(0.32-0.41)低于小鼠皮肤(1.07-1.21)。ADH抑制剂4-甲基吡唑(4-MP)以浓度依赖的方式减少皮肤和肝脏的乙醇氧化：使用1 mM的4-MP，皮肤和肝脏的活性分别降至对照活性的约30-40%和约2-10%。ADH和ALDH酶在皮肤和肝脏中的类特异性表达以及它们在物种之间的变化，可能对内源和外源酒精和醛的代谢具有毒理学意义。(C)2002爱思唯尔科学爱尔兰有限公司。保留所有权利。
Alcohol dehydrogenase (ADH; EC. 1. 1. 1. 1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) play important roles in the metabolism of both endogenous and exogenous alcohols and aldehydes. The expression and localisation patterns of ADH (1 -3) and ALDH (1 -3) were investigated in the skin and liver of the mouse (BALB/c and CBA/ca), rat (17344) and guinea-pig (Dunkin-Hartley), using Western blot analysis and immunohistochemistry with class-specific antisera. ALDH2 expression and localisation was also determined in human skin, while ethanol oxidation, catalysed by ADH, was investigated in-the mouse, guinea-pig and human skin cytosol. Western blot analysis revealed that ADH 1, ADH3, ALDH I and ALDH2 were expressed, constitutively, in the skin and liver of the mouse, rat and guinea-pig. ADH2 was not detected in the skin of any rodent species/strain, but was present in all rodent livers. ALDH3 was expressed, constitutively, in the skin of both strains of mouse and rat, but was not detected in guinea-pig skin and was absent in all livers. Immumohistochemistry showed similar patterns of expression for ADH and ALDH in both strains of mouse, rat, guinea-pig and human skin sections, with localisation predominantly in the epidermis, sebaceous glands and hair follicles. ADH activity (apparent V-max, nmoles/mg protein/min) was higher in liver (6.02-16.67) compared to skin (0.32-1.21) and lower in human skin (0.32-0.41) compared to mouse skin (1.07-1.21). The ADH inhibitor 4-methyl pyrazole (4-MP) reduced ethanol oxidation in the skin and liver in a concentration dependent manner: activity was reduced to approximate to 30-40% and approximate to 2-10% of the control activity, in the skin and liver, respectively, using 1 mM 4-MP. The class-specific expression of ADH and ALDH enzymes, in the skin and liver and their variation between species, may have toxicological significance, with respect to the metabolism of endogenous and xenobiotic alcohols and aldehydes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.