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 language | English (US) |
|---|---|
| Pages (from-to) | H2637-H2645 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 294 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2008 |
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Keywords
- Coronary ligation
- Cytochrome oxidase subunit
- Mitochondria
- Preconditioning
- Protein kinase C
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury : Exacerbation of COI subunit loss by PKC-ε inhibition. / Yu, Qilin; Nguyen, Tiffany; Ogbi, Mourad; Caldwell, Robert W.; Johnson, John A.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 294, No. 6, 01.06.2008, p. H2637-H2645.Research output: Contribution to journal › Article
}
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 W.
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
UR - http://www.scopus.com/inward/record.url?scp=49249102227&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49249102227&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.91476.2007
DO - 10.1152/ajpheart.91476.2007
M3 - Article
C2 - 18408135
AN - SCOPUS:49249102227
VL - 294
SP - H2637-H2645
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 6
ER -