Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer.
Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer.
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DOI：
10.1007/978-3-319-98788-0_14
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发表时间：
2018
影响因子：
--
通讯作者：
Vasiliou V
中科院分区：
文献类型：
--
作者：
Marshall S;Chen Y;Singh S;Berrios-Carcamo P;Heit C;Apostolopoulos N;Golla JP;Thompson DC;Vasiliou V
在世界范围内，过度饮酒是由生活方式引起的发病和死亡的一个主要原因。尽管长期酗酒已被证明对肝脏、大脑和许多其他器官有害，但我们对这种情况发生的确切分子机制的了解仍然有限。在组织中，乙醇代谢为乙醛（主要通过乙醇脱氢酶和细胞色素p450 2E1），随后通过醛脱氢酶代谢为乙酸。细胞内自由基的产生和抗氧化剂谷胱甘肽（GSH）的消耗被认为是乙醇引起的细胞致病性事件的关键步骤。随着持续过量饮酒，细胞蛋白质和DNA加合物的产生可能导致进一步的组织损伤，这些加合物是由乙醇衍生的醛积累引起的。我们对乙醇代谢的病理生理后果的理解大部分来自乙醇诱导组织损伤的基因工程小鼠模型。在这篇综述中，我们提供了当前对重要小鼠模型的最新理解，在这些模型中，乙醇代谢和谷胱甘肽合成酶被操纵来研究酒精诱导的疾病。
Excessive consumption of alcohol is a leading cause of lifestyle-induced morbidity and mortality worldwide. Although long-term alcohol abuse has been shown to be detrimental to the liver, brain and many other organs, our understanding of the exact molecular mechanisms by which this occurs is still limited. In tissues, ethanol is metabolized to acetaldehyde (mainly by alcohol dehydrogenase and cytochrome p450 2E1) and subsequently to acetic acid by aldehyde dehydrogenases. Intracellular generation of free radicals and depletion of the antioxidant glutathione (GSH) are believed to be key steps involved in the cellular pathogenic events caused by ethanol. With continued excessive alcohol consumption, further tissue damage can result from the production of cellular protein and DNA adducts caused by accumulating ethanol-derived aldehydes. Much of our understanding about the pathophysiological consequences of ethanol metabolism comes from genetically-engineered mouse models of ethanol-induced tissue injury. In this review, we provide an update on the current understanding of important mouse models in which ethanol-metabolizing and GSH-synthesizing enzymes have been manipulated to investigate alcohol-induced disease.
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DOI：
10.1111/acer.12777
发表时间：
2015-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Chaudhry KK;Samak G;Shukla PK;Mir H;Gangwar R;Manda B;Isse T;Kawamoto T;Salaspuro M;Kaihovaara P;Dietrich P;Dragatsis I;Nagy LE;Rao RK
通讯作者：
Rao RK
影响因子：
25.7
作者：
Chen Y;Johansson E;Yang Y;Miller ML;Shen D;Orlicky DJ;Shertzer HG;Vasiliou V;Nebert DW;Dalton TP
通讯作者：
Dalton TP
影响因子：
2.3
作者：
Husain, K;Scott, BR;Somani, SA
通讯作者：
Somani, SA
影响因子：
4.8
作者：
Ho, YS;Xiong, Y;Ho, DS
通讯作者：
Ho, DS
DOI：
10.1111/j.1530-0277.2008.00780.x
发表时间：
2008-11-01
影响因子：
3.2
作者：
Husemoen, Lise Lotte Nystrup;Fenger, Mogens;Linneberg, Allan
通讯作者：
Linneberg, Allan