Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury: Exacerbation of COI subunit loss by PKC-ε inhibition

Qilin Yu, Tiffany Nguyen, Mourad Ogbi, Robert W. Caldwell, John A. Johnson

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

We have previously described a PKC-ε interaction with cytochrome oxidase subunit IV (COIV) that correlates with enhanced CO activity and cardiac ischemic preconditioning (PC). We therefore investigated the effects of PC and ischemia-reperfusion (I/R) injury on CO subunit levels in an anesthetized rat coronary ligation model. Homogenates prepared from the left ventricular regions at risk (RAR) and not at risk (RNAR) for I/R injury were fractionated into cell-soluble (S), 600 g low-speed centrifugation (L), gradient-purified mitochondrial (M), and 100,000 g particulate (P) fractions. In RAR tissue, PC (2 cycles of 5-min ischemia and 5-min reperfusion) decreased the COI in the P fraction (∼29% of total cellular COI), suggesting changes in interfibrillar mitochondria. After 30 min of ischemia and 120 min of reperfusion, total COI levels decreased in the RAR by 72%. Subunit Va was also downregulated by 42% following prolonged I/R in the RAR. PC administered before I/R reduced the loss of COI in the M and P fractions ∼30% and prevented COVa losses completely. We observed no losses in subunits Vb and VIIa following I/R alone; however, significant losses occurred when PC was administered before prolonged I/R. Delivery of a cell-permeable PKC-ε translocation inhibitor (εV1-2) to isolated rat hearts before prolonged I/R dramatically increased COI loss, suggesting that PKC-ε protects COI levels. We propose that additional measures to protect CO subunits when coadministered with PC may improve its cardioprotection against I/R injury.

Original languageEnglish (US)
Pages (from-to)H2637-H2645
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Coronary ligation
  • Cytochrome oxidase subunit
  • Mitochondria
  • Preconditioning
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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