Translocation of δPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function

Eric N. Churchill, Luke I. Szweda

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Activation of the δ-isoform of protein kinase C (δPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced δPKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O2-.) generation. This was associated with the translocation of δPKC to the mitochondria within the first 5 min of reperfusion. δPKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H2O 2 suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (δV1-1) specific to the δ-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O2-. generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120 min) was completely prevented by inhibition of δPKC translocation. Thus, δPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O2-. production and subsequent declines in mitochondrial function during reperfusion.

Original languageEnglish (US)
Pages (from-to)194-199
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume439
Issue number2
DOIs
StatePublished - Jul 15 2005

Fingerprint

Mitochondria
Superoxides
Protein Kinase C
Reperfusion
Oxidation-Reduction
Protein Isoforms
Chemical activation
Heart Mitochondria
Myocardial Reperfusion
Oxidative stress
Cytochromes c
Amplification
Oxidative Stress
Phosphotransferases
Ischemia
Apoptosis
Peptides
Molecules

Keywords

  • Free radical
  • Heart
  • Ischemia
  • Mitochondria
  • PKC
  • Reperfusion
  • Respiration

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Translocation of δPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function",
abstract = "Activation of the δ-isoform of protein kinase C (δPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced δPKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O2-.) generation. This was associated with the translocation of δPKC to the mitochondria within the first 5 min of reperfusion. δPKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H2O 2 suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (δV1-1) specific to the δ-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O2-. generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120 min) was completely prevented by inhibition of δPKC translocation. Thus, δPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O2-. production and subsequent declines in mitochondrial function during reperfusion.",
keywords = "Free radical, Heart, Ischemia, Mitochondria, PKC, Reperfusion, Respiration",
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AU - Churchill, Eric N.

AU - Szweda, Luke I.

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N2 - Activation of the δ-isoform of protein kinase C (δPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced δPKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O2-.) generation. This was associated with the translocation of δPKC to the mitochondria within the first 5 min of reperfusion. δPKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H2O 2 suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (δV1-1) specific to the δ-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O2-. generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120 min) was completely prevented by inhibition of δPKC translocation. Thus, δPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O2-. production and subsequent declines in mitochondrial function during reperfusion.

AB - Activation of the δ-isoform of protein kinase C (δPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced δPKC translocation on mitochondrial function were assessed. Mitochondria isolated from hearts that had undergone ischemia (30 min) followed by reperfusion (15 min) exhibited a significant increase in the rate of superoxide anion (O2-.) generation. This was associated with the translocation of δPKC to the mitochondria within the first 5 min of reperfusion. δPKC translocation occurred exclusively during reperfusion and could be mimicked by infusion of intact hearts with H2O 2 suggesting redox-dependent activation during reperfusion. Infusion of a peptide inhibitor (δV1-1) specific to the δ-isoform of PKC significantly reduced reperfusion-induced increases in mitochondrial O2-. generation. Finally, the decline in mitochondrial respiratory activity evident upon prolonged reperfusion (120 min) was completely prevented by inhibition of δPKC translocation. Thus, δPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O2-. production and subsequent declines in mitochondrial function during reperfusion.

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