Proteomic and metabolomic analysis of cardioprotection: Interplay between protein kinase C epsilon and delta in regulating glucose metabolism of murine hearts

Manuel Mayr, David Liem, Jun Zhang, Xiaohai Li, Nuraly K. Avliyakulov, Jeong In Yang, Glen Young, Tom M. Vondriska, Christophe Ladroue, Basetti Madhu, John R. Griffiths, Aldrin V Gomes, Qingbo Xu, Peipei Ping

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65 Scopus citations

Abstract

We applied a combined proteomic and metabolomic approach to obtain novel mechanistic insights in PKCe{open}-mediated cardioprotection. Mitochondrial and cytosolic proteins from control and transgenic hearts with constitutively active or dominant negative PKCe{open} were analyzed using difference in-gel electrophoresis (DIGE). Among the differentially expressed proteins were creatine kinase, pyruvate kinase, lactate dehydrogenase, and the cytosolic isoforms of aspartate amino transferase and malate dehydrogenase, the two enzymatic components of the malate aspartate shuttle, which are required for the import of reducing equivalents from glycolysis across the inner mitochondrial membrane. These enzymatic changes appeared to be dependent on PKCe{open} activity, as they were not observed in mice expressing inactive PKCe{open}. High-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy confirmed a pronounced effect of PKCe{open} activity on cardiac glucose and energy metabolism: normoxic hearts with constitutively active PKCe{open} had significantly lower concentrations of glucose, lactate, glutamine and creatine, but higher levels of choline, glutamate and total adenosine nucleotides. Moreover, the depletion of cardiac energy metabolites was slower during ischemia/reperfusion injury and glucose metabolism recovered faster upon reperfusion in transgenic hearts with active PKCe{open}. Notably, inhibition of PKCe{open} resulted in compensatory phosphorylation and mitochondrial translocation of PKCδ. Taken together, our findings are the first evidence that PKCe{open} activity modulates cardiac glucose metabolism and provide a possible explanation for the synergistic effect of PKCδ and PKCe{open} in cardioprotection.

Original languageEnglish (US)
Pages (from-to)268-277
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume46
Issue number2
DOIs
StatePublished - Feb 2009

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Keywords

  • Cardioprotection
  • Metabolism
  • Mitochondria
  • Preconditioning
  • Protein kinase C
  • Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Mayr, M., Liem, D., Zhang, J., Li, X., Avliyakulov, N. K., Yang, J. I., Young, G., Vondriska, T. M., Ladroue, C., Madhu, B., Griffiths, J. R., Gomes, A. V., Xu, Q., & Ping, P. (2009). Proteomic and metabolomic analysis of cardioprotection: Interplay between protein kinase C epsilon and delta in regulating glucose metabolism of murine hearts. Journal of Molecular and Cellular Cardiology, 46(2), 268-277. https://doi.org/10.1016/j.yjmcc.2008.10.008