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

American Journal of Physiology. Heart and Circulatory Physiology
Qilin YuJ A Johnson

Abstract

We have previously described a PKC-epsilon 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 ( approximately 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 approximately 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 prolonge...Continue Reading

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Citations

Sep 2, 2010·Cardiovascular Research·Marjan Gucek, Elizabeth Murphy
Oct 27, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Renee WongElizabeth Murphy
Feb 4, 2011·American Journal of Physiology. Renal Physiology·Grazyna NowakAllen M Samarel
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Jun 15, 2011·Mitochondrion·Alena PecinováJosef Houštěk
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Mar 1, 2014·Circulation Research·Karin PrzyklenkMaik Hüttemann
Apr 20, 2011·Expert Review of Proteomics·Hyoung Kyu KimJin Han
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Apr 30, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Edoardo BerteroJan Dudek
Jun 9, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Li ChenMing Guo

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