کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2563626 | 1127548 | 2011 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
ALDH2 in alcoholic heart diseases: Molecular mechanism and clinical implications
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کلمات کلیدی
ALDHMMPsarco(endo)plasmic reticulum Ca2+-ATPase4-HNECYP2E1GTNALDH2DAPTHUVECADH4-hydroxy-2-nonenal - 4-هیدروکسی-2 غیرنالNAD+ - NAD +ROS - ROSaldehyde dehydrogenase - آلدئید دهیدروژنازEnzyme - آنزیم یا کاتالیزگرAlcohol - الکلAlcohol dehydrogenase - الکل دهیدروژنازSarcoplasmic reticulum - رتیکولوم سارکوپلاسمیکHuman umbilical vein endothelial cells - سلول های اندوتلیالی ورید ناف انسانcytochrome P450 2E1 - سیتوکروم P450 2E1endoplasmic reticulum - شبکه آندوپلاسمی SERCA - قلبMetabolism - متابولیسم Transgenic mice - موش ترانس ژنیکmyocardial - میوکاردNAD, nicotinamide adenine dinucleotide - نیکوتینامید آدنین دینوکلئوتیدMitochondrial membrane potential - پتانسیل غشای میتوکندریGlyceryl trinitrate - گلیسریل ترنیتاتReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
Alcoholic cardiomyopathy is manifested as cardiac hypertrophy, disrupted contractile function and myofibrillary architecture. An ample amount of clinical and experimental evidence has depicted a pivotal role for alcohol metabolism especially the main alcohol metabolic product acetaldehyde, in the pathogenesis of this myopathic state. Findings from our group and others have revealed that the mitochondrial isoform of aldehyde dehydrogenase (ALDH2), which metabolizes acetaldehyde, governs the detoxification of acetaldehyde formed following alcohol consumption and the ultimate elimination of alcohol from the body. The ALDH2 enzymatic cascade may evolve as a unique detoxification mechanism for environmental alcohols and aldehydes to alleviate the undesired cardiac anomalies in ischemia-reperfusion and alcoholism. Polymorphic variants of the ALDH2 gene encode enzymes with altered pharmacokinetic properties and a significantly higher prevalence of cardiovascular diseases associated with alcoholism. The pathophysiological effects of ALDH2 polymorphism may be mediated by accumulation of acetaldehyde and other reactive aldehydes. Inheritance of the inactive ALDH2*2 gene product is associated with a decreased risk of alcoholism but an increased risk of alcoholic complications. This association is influenced by gene-environment interactions such as those associated with religion and national origin. The purpose of this review is to recapitulate the pathogenesis of alcoholic cardiomyopathy with a special focus on ALDH2 enzymatic metabolism. It will be important to dissect the links between ALDH2 polymorphism and prevalence of alcoholic cardiomyopathy, in order to determine the mechanisms underlying such associations. The therapeutic value of ALDH2 as both target and tool in the management of alcoholic tissue damage will be discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 132, Issue 1, October 2011, Pages 86-95
Journal: Pharmacology & Therapeutics - Volume 132, Issue 1, October 2011, Pages 86-95
نویسندگان
Yingmei Zhang, Jun Ren,