Document Detail


Chronic Ethanol Consumption Increases Myocardial Mitochondrial DNA Mutations: A Potential Contribution by Mitochondrial Topoisomerases.
MedLine Citation:
PMID:  24852753     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is known to have a significant role in the development and complications of ACM. This study investigated if chronic ethanol feeding promoted myocardial mitochondrial topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA) damage and mitochondrial dysfunction in ACM.
METHODS: The impact of chronic ethanol exposure on the myocardial mitochondria was examined in both neonatal cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or ethanol feeding groups for 4 months.
RESULTS: Chronic ethanol feeding led to significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection fraction, and the cardiac output index as well as increases in Tau. Ethanol feeding promoted mitochondrial dysfunction as evidenced by significantly decreased left ventricle cytochrome oxidase activity and decreases in mitochondrial protein content. Both in rats and in cultured cardiomyocytes, chronic ethanol presentation significantly increased mtDNA damage. Using isolated myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage and DNA relaxation were significantly altered by ethanol feeding.
CONCLUSION: Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.
Authors:
D Laurent; J E Mathew; M Mitry; M Taft; A Force; J G Edwards
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-22
Journal Detail:
Title:  Alcohol and alcoholism (Oxford, Oxfordshire)     Volume:  -     ISSN:  1464-3502     ISO Abbreviation:  Alcohol Alcohol.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8310684     Medline TA:  Alcohol Alcohol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.
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