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 William Caldwell, John A Johnson

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28 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number6
DOIs
StatePublished - Jun 1 2008

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Electron Transport Complex IV
Reperfusion Injury
Reperfusion
Ischemia
Carbon Monoxide
Ischemic Preconditioning
Centrifugation
Ligation
Mitochondria
Down-Regulation

Keywords

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

ASJC Scopus subject areas

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

Cite this

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title = "Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury: Exacerbation of COI subunit loss by PKC-ε inhibition",
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.",
keywords = "Coronary ligation, Cytochrome oxidase subunit, Mitochondria, Preconditioning, Protein kinase C",
author = "Qilin Yu and Tiffany Nguyen and Mourad Ogbi and Caldwell, {Robert William} and Johnson, {John A}",
year = "2008",
month = "6",
day = "1",
doi = "10.1152/ajpheart.91476.2007",
language = "English (US)",
volume = "294",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
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TY - JOUR

T1 - Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury

T2 - Exacerbation of COI subunit loss by PKC-ε inhibition

AU - Yu, Qilin

AU - Nguyen, Tiffany

AU - Ogbi, Mourad

AU - Caldwell, Robert William

AU - Johnson, John A

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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.

AB - 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.

KW - Coronary ligation

KW - Cytochrome oxidase subunit

KW - Mitochondria

KW - Preconditioning

KW - Protein kinase C

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JO - American Journal of Physiology - Heart and Circulatory Physiology

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