Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts

Carmen P. Lydell, Andy Chan, Richard B. Wambolt, Nandakumar Sambandam, Hannah Parsons, Gregory P. Bondy, Brian Rodrigues, Kirill M. Popov, Robert A. Harris, Roger W. Brownsey, Michael F. Allard

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53 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)841-851
Number of pages11
JournalCardiovascular research
Volume53
Issue number4
DOIs
StatePublished - Apr 9 2002

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Keywords

  • Energy metabolism
  • Gene expression
  • Glycolysis
  • Hypertrophy
  • Protein phosphorylation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lydell, C. P., Chan, A., Wambolt, R. B., Sambandam, N., Parsons, H., Bondy, G. P., Rodrigues, B., Popov, K. M., Harris, R. A., Brownsey, R. W., & Allard, M. F. (2002). Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts. Cardiovascular research, 53(4), 841-851. https://doi.org/10.1016/S0008-6363(01)00560-0