Document Detail


Impact of altered methylation in cytokine signaling and proteasome function in alcohol and viral-mediated diseases.
MedLine Citation:
PMID:  22577887     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Data from several laboratories have shown that ethanol (EtOH) feeding impairs many essential methylation reactions that contribute to alcoholic liver disease (ALD). EtOH is also a comorbid factor in the severity of hepatitis C virus-induced liver injury. The presence of viral proteins further exacerbates the methylation defects to disrupt multiple pathways that promote the pathogenesis of liver disease. This review is a compilation of presentations that linked the methylation reaction defects with proteasome inhibition, decreased antigen presentation, and impaired interferon (IFN) signaling in the hepatocytes and dysregulated TNFα expression in macrophages. Two therapeutic modalities, betaine and S-adenosylmethionine, can correct methylation defects to attenuate many EtOH-induced liver changes, as well as improve IFN signaling pathways, thereby overcoming viral treatment resistance.
Authors:
Kusum K Kharbanda; Fawzia Bardag-Gorce; Shirish Barve; Patricia E Molina; Natalia A Osna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2012-05-11
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  37     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-06-28     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 by the Research Society on Alcoholism.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation
Betaine / pharmacology
Ethanol / adverse effects*
Hepatitis C / complications*
Humans
Interferons / metabolism
Liver / metabolism,  pathology
Liver Diseases, Alcoholic / complications,  enzymology*
Methionine / metabolism
Methylation
Methyltransferases / antagonists & inhibitors,  metabolism*
Proteasome Endopeptidase Complex / metabolism*
S-Adenosylmethionine / pharmacology
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
AA014371/AA/NIAAA NIH HHS; AA017232/AA/NIAAA NIH HHS; AA017296/AA/NIAAA NIH HHS; AA018016/AA/NIAAA NIH HHS; AA07577/AA/NIAAA NIH HHS; AA09803/AA/NIAAA NIH HHS; AA11290/AA/NIAAA NIH HHS; R01 AA018869/AA/NIAAA NIH HHS; R21 AA017232-01A2/AA/NIAAA NIH HHS; R21 AA017296/AA/NIAAA NIH HHS; R21 AA017296-01A1/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Tumor Necrosis Factor-alpha; 3K9958V90M/Ethanol; 3SCV180C9W/Betaine; 7LP2MPO46S/S-Adenosylmethionine; 9008-11-1/Interferons; AE28F7PNPL/Methionine; EC 2.1.1.-/Methyltransferases; EC 3.4.25.1/Proteasome Endopeptidase Complex
Comments/Corrections

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