Delta protein kinase C interacts with the d subunit of the F 1F0 ATPase in neonatal cardiac myocytes exposed to hypoxia or phorbol ester: Implications for F1F0 ATPase regulation

Tiffany Nguyen, Mourad Ogbi, John A. Johnson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Mitochondrial protein kinase C isozymes have been reported to mediate both cardiac ischemic preconditioning and ischemia/reperfusion injury. In addition, cardiac preconditioning improves the recovery of ATP levels after ischemia/reperfusion injury. We have, therefore, evaluated protein kinase C modulation of the F1F0 ATPase in neonatal cardiac myocytes. Exposure of cells to 3 or 100 nM 4β-phorbol 12-myristate-13- acetate induced co-immunoprecipitation of δ protein kinase C (but not α, ε, or ζ protein kinase C) with the d subunit of the F 1F0 ATPase. This co-immunoprecipitation correlated with 40 ± 3% and 72- ± 9% inhibitions of oligomycin-sensitive F 1F0 ATPase activity, respectively. We observed prominent expression of δ protein kinase C in cardiac myocyte mitochondria, which was enhanced following a 4-h hypoxia exposure. In contrast, hypoxia decreased mitochondrial ζPKC levels by 85 ± -1%. Following 4 h of hypoxia, F1F0 ATPase activity was inhibited by 75 ± -9% and δ protein kinase C co-immunoprecipitated with the d subunit of F 1F0 ATPase. In vitro incubation of protein kinase C with F1F0 ATPase enhanced F1F0 activity in the absence of protein kinase C activators and inhibited it in the presence of activators. Recombinant δ protein kinase C also inhibited F 1F0 ATPase activity. Protein kinase C overlay assays revealed δ protein kinase C binding to the d subunit of F 1F0 ATPase, which was modulated by diacylglycerol, phosphatidylserine, and cardiolipin. Our results suggest a novel regulation of the F1F0 ATPase by the δ protein kinase C isozyme.

Original languageEnglish (US)
Pages (from-to)29831-29840
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number44
DOIs
StatePublished - Oct 31 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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