Document Detail

Effects of perhexiline-induced fuel switch on the cardiac proteome and metabolome.
MedLine Citation:
PMID:  23277191     Owner:  NLM     Status:  MEDLINE    
Perhexiline is a potent anti-anginal drug used for treatment of refractory angina and other forms of heart disease. It provides an oxygen sparing effect in the myocardium by creating a switch from fatty acid to glucose metabolism through partial inhibition of carnitine palmitoyltransferase 1 and 2. However, the precise molecular mechanisms underlying the cardioprotective effects elicited by perhexiline are not fully understood. The present study employed a combined proteomics, metabolomics and computational approach to characterise changes in murine hearts upon treatment with perhexiline. According to results based on difference in-gel electrophoresis, the most profound change in the cardiac proteome related to the activation of the pyruvate dehydrogenase complex. Metabolomic analysis by high-resolution nuclear magnetic resonance spectroscopy showed lower levels of total creatine and taurine in hearts of perhexiline-treated mice. Creatine and taurine levels were also significantly correlated in a cross-correlation analysis of all metabolites. Computational modelling suggested that far from inducing a simple shift from fatty acid to glucose oxidation, perhexiline may cause complex rebalancing of carbon and nucleotide phosphate fluxes, fuelled by increased lactate and amino acid uptake, to increase metabolic flexibility and to maintain cardiac output. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
Xiaoke Yin; Joseph Dwyer; Sarah R Langley; Ursula Mayr; Qiuru Xing; Ignat Drozdov; Adam Nabeebaccus; Ajay M Shah; Basetti Madhu; John Griffiths; Lindsay M Edwards; Manuel Mayr
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-29
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  55     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-03     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  27-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Cardiovascular Agents / pharmacology*
Cluster Analysis
Computer Simulation
Heart / drug effects*
Models, Biological
Myocardium / metabolism*
Perhexiline / pharmacology*
Grant Support
RG/08/011/25922//British Heart Foundation; //British Heart Foundation
Reg. No./Substance:
0/Cardiovascular Agents; 0/Proteome; KU65374X44/Perhexiline

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