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 language | English (US) |
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Pages (from-to) | 194-199 |
Number of pages | 6 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 439 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2005 |
Keywords
- Free radical
- Heart
- Ischemia
- Mitochondria
- PKC
- Reperfusion
- Respiration
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology