Document Detail


Metabolic inflexibility and protein lysine acetylation in heart mitochondria of a chronic model of type 1 diabetes.
MedLine Citation:
PMID:  23030792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diabetic cardiomyopathy refers to the changes in contractility that occur to the diabetic heart that can arise in the absence of vascular disease. Mitochondrial bioenergetic deficits and increased free radical production are pathological hallmarks of diabetic cardiomyopathy, but the mechanisms and causal relationships between mitochondrial deficits and the progression of disease are not understood. We evaluated cardiac mitochondrial function in a rodent model of chronic Type 1 diabetes (OVE26 mice) before the onset of contractility deficits. We found that the most pronounced change in OVE26 heart mitochondria is severe metabolic inflexibility. This inflexibility is characterized by large deficits in mitochondrial respiration measured in the presence of non-fatty acid substrates. Metabolic inflexibility occurred concomitantly with decreased activities of PDH (pyruvate dehydrogenase) and complex II. Hyper-acetylation of protein lysine was also observed. Treatment of control heart mitochondria with acetic anhydride (Ac2O), an acetylating agent, preferentially inhibited respiration by non-fatty acid substrates and increased superoxide production. We have concluded that metabolic inflexibility, induced by discrete enzymatic and molecular changes, including hyper-acetylation of protein lysine residues, precedes mitochondrial defects in a chronic rodent model of Type 1 diabetes.
Authors:
Shraddha S Vadvalkar; C Nathan Baily; Satoshi Matsuzaki; Melinda West; Yasvir A Tesiram; Kenneth M Humphries
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Biochemical journal     Volume:  449     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-08     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  253-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Animals
Chronic Disease
Diabetes Mellitus, Type 1 / metabolism*,  pathology
Diabetic Cardiomyopathies / metabolism*,  pathology
Disease Models, Animal*
Lysine / chemistry,  metabolism*
Male
Mice
Mitochondria, Heart / metabolism*,  pathology
Grant Support
ID/Acronym/Agency:
P20 RR 024215/RR/NCRR NIH HHS; P20 RR024215/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
K3Z4F929H6/Lysine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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