Ethanol induces skin hyperpigmentation in mice with aldehyde dehydrogenase 2 deficiency
Ethanol induces skin hyperpigmentation in mice with aldehyde dehydrogenase 2 deficiency
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DOI：
10.1016/j.cbi.2019.01.035
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发表时间：
2019-04-01
影响因子：
5.1
通讯作者：
Fujita, Mayumi
中科院分区：
文献类型：
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作者：
Matsumoto, Akiko;Ito, Shosuke;Fujita, Mayumi
酒精会引起各种皮肤变化，如手掌红斑和黄疸。然而，由于黑色素沉积而导致的酒精引起的皮肤色素沉着尚未见报道。乙醛脱氢酶2(ALDH2)是人类19种ALDH同工酶之一，能将内源和外源醛代谢成相应的羧酸。降低的ALDH2极大地影响乙醛的新陈代谢，导致其在饮酒后在体内积累，并随之而来的一系列表型的发展。在本研究中，我们报告了一种新的表型，在ALDH2表达改变的小鼠模型中表现出来。ALDH2基因敲除小鼠(ALDH2+/-和ALDH2-/-)和野生型(ALDH2+/+)小鼠分别以标准固体食物和一瓶浓度为0%、3%、10%或20%(v/v)的乙醇溶液喂养10周以上。通过肉眼观察评价皮肤色素沉着的强度。酒精暴露的ALDH2+/-和ALDH2-/-小鼠在无毛皮肤区域表现出剂量依赖性的皮肤色素沉着，包括爪底和尾巴；在野生型小鼠中没有观察到这种变化。皮肤色素沉着的强度与小鼠ALDH2+/+、ALDH2+/-和ALDH2-/-的等位基因改变的数量相关(即ALDH2+/+、ALDH2+/-和ALDH2-/-的等位基因分别为0、1和2)。有趣的是，停止使用乙醇后，皮肤色素沉着的变化发生了逆转。皮肤色素沉着的组织学检查显示存在黑色素样沉积，主要在表皮。总之，我们报告了一项新的发现，摄入乙醇以一种ALDH2活性依赖的方式诱导皮肤色素沉着。
Alcohol induces various cutaneous changes, such as palmar erythema and jaundice. However, alcohol-induced skin hyperpigmentation due to melanin deposition has not been reported. Aldehyde dehydrogenase 2 (ALDH2), one of 19 human ALDH isozymes, metabolizes endogenous and exogenous aldehydes to their respective carboxylic acids. Reduced ALDH2 greatly affects acetaldehyde metabolism, leading to its accumulation in the body after the consumption of alcohol and the consequent development of a wide range of phenotypes. In the present study, we report a novel phenotype manifesting in a mouse model with the altered expression of ALDH2. Aldh2 knockout (Aldh2+/- and Aldh2-/-) and wild-type (Aldh2+/+) mice were fed a standard solid rodent chow and a bottle of ethanol solution at concentrations of 0%, 3%, 10%, or 20% (v/v) for more than 10 weeks. The intensity of their skin pigmentation was evaluated by macroscopic observation. Ethanol-exposed Aldh2+/- and Aldh2-/- mice exhibited dose-dependent skin pigmentation in areas of hairless skin, including the soles of the paws and tail; no such changes were observed in wild-type mice. The intensity of skin pigmentation correlated with the number of Aldh2 alleles that were altered in the mice (i.e., 0, 1 and 2 for Aldh2+/+, Aldh2+/-, Aldh2-/-, respectively). Interestingly, the skin pigmentation changes reversed upon the discontinuation of ethanol. The histological examination of the pigmented skin demonstrated the presence of melanin-like deposits, mainly in the epidermis. In conclusion, we report a novel finding that the intake of ethanol induces skin hyperpigmentation in an ALDH2 activity-dependent manner.