© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts
aMcDonald Research Laboratories/The iCapture Centre, Department of Pathology and Laboratory Medicine, Room 292, University of British Columbia–St. Paul's Hospital, 1081 Burrand Street, Vancouver, BC, Canada V6Z 1Y6
bDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
cDepartment of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
dDivision of Molecular Biology and Biochemistry, University of Missouri at Kansas City, Kansas City, MO 64110, USA
eDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202-5122, USA
* Corresponding author. Tel.: +1-604-682-2344x62570; fax: +1-604-806-8351 mallard{at}mrl.ubc.ca
Objective: Coupling of glucose oxidation to glycolysis is lower in hypertrophied than in non-hypertrophied hearts, contributing to the compromised mechanical performance of hypertrophied hearts. Here, we describe studies to test the hypothesis that low coupling of glucose oxidation to glycolysis in hypertrophied hearts is due to reduced activity and/or expression of the pyruvate dehydrogenase complex (PDC). Methods: We examined the effects of dichloroacetate (DCA), an inhibitor of PDC kinase, and of alterations in exogenous palmitate supply on coupling of glucose oxidation to glycolysis in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague–Dawley rats. It was anticipated that the addition of DCA or the absence of palmitate would promote PDC activation and consequently normalize coupling between glycolysis and glucose oxidation in hypertrophied hearts if our hypothesis was correct. Results: Addition of DCA or removal of palmitate improved coupling of glucose oxidation to glycolysis in control and hypertrophied hearts. However, coupling remained substantially lower in hypertrophied hearts. PDC activity in extracts of hypertrophied hearts was similar to or higher than in extracts of control hearts under all perfusion conditions. No differences were observed between hypertrophied and control hearts with respect to expression of PDC, PDC kinase, or PDC phosphatase. Conclusions: Low coupling of glucose oxidation to glycolysis in hypertrophied hearts is not due to a reduction in PDC activity or subunit expression indicating that other mechanism(s) are responsible.
KEYWORDS Energy metabolism; Gene expression; Glycolysis; Hypertrophy; Protein phosphorylation
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