Differential loss of cytochrome-<i>c</i>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.

doi:10.1152/ajpheart.91476.2007

Cited by 30 publications

(24 citation statements)

References 60 publications

(98 reference statements)

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“…However, PKC-ε activation is not protective in all cell types. Our data are in contrast with the observation in ischemic cardiac tissue and neonatal cardiomyocytes demonstrating that the association of PKC-ε with cytochrome oxidase (complex IV) results in a twofold increase in cytochrome oxidase activity and in the brain where PKC-ε activation improves mitochondrial functions (12,19,37,38,54). Our data are also in contrast to the observation in lens mitochondria where PKC-ε activated by hypoxia colocalizes and associates with cytochrome oxidase and increases its activity (4).…”

Section: Discussioncontrasting

confidence: 99%

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

Nowak

Bakajsova

Samarel

2011

American Journal of Physiology-Renal Physiology

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PKC-ε activation mediates protection from ischemia-reperfusion injury in the myocardium. Mitochondria are a subcellular target of these protective mechanisms of PKC-ε. Previously, we have shown that PKC-ε activation is involved in mitochondrial dysfunction in oxidant-injured renal proximal tubular cells (RPTC; Nowak G, Bakajsova D, Clifton GL Am J Physiol Renal Physiol 286: F307–F316, 2004). The goal of this study was to examine the role of PKC-ε activation in mitochondrial dysfunction and to identify mitochondrial targets of PKC-ε in RPTC. The constitutively active and inactive mutants of PKC-ε were overexpressed in primary cultures of RPTC using the adenoviral technique. Increases in active PKC-ε levels were accompanied by PKC-ε translocation to mitochondria. Sustained PKC-ε activation resulted in decreases in state 3 respiration, electron transport rate, ATP production, ATP content, and activities of complexes I and IV and F0F1-ATPase. Furthermore, PKC-ε activation increased mitochondrial membrane potential and oxidant production and induced mitochondrial fragmentation and RPTC death. Accumulation of the dynamin-related protein in mitochondria preceded mitochondrial fragmentation. Antioxidants blocked PKC-ε-induced increases in the oxidant production but did not prevent mitochondrial fragmentation and cell death. The inactive PKC-ε mutant had no effect on mitochondrial functions, morphology, oxidant production, and RPTC viability. We conclude that active PKC-ε targets complexes I and IV and F0F1-ATPase in RPTC. PKC-ε activation mediates mitochondrial dysfunction, hyperpolarization, and fragmentation. It also induces oxidant generation and cell death, but oxidative stress is not the mechanism of RPTC death. These results show that in contrast to protective effects of PKC-ε activation in cardiomyocytes, sustained PKC-ε activation is detrimental to mitochondrial function and viability in RPTC.

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Section: Discussioncontrasting

confidence: 99%

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

Nowak

Bakajsova

Samarel

2011

American Journal of Physiology-Renal Physiology

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“…6) The serine/threonine protein kinase Cε (PKCε) binds to COX subunit IV and phosphorylates it (Ogbi and Johnson, 2006;Ogbi et al, 2004). In a further study it was concluded that PKCε may interact with COX subunit IV as a component of the cardioprotection in ischemic preconditioning (Guo et al, 2007;Yu et al, 2008;Vogtle et al, 2012). 7) Finally, in neonatal rat cardiomyocytes, under hypoxic conditions, the expression of the hypoxia inducible domain family,member 1A (Higd1a) was identified.…”

Section: Number Of Subunits In Mammalian Coxmentioning

confidence: 99%

The subunit composition and function of mammalian cytochrome c oxidase

2015

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“…A previous study from our laboratory showed a steady and notable loss of subunits I, IVI1, and Vb under chemical stress, hypoxia, and myocardial ischemia/ reperfusion conditions (28,31,32). Others have shown lowering of subunits I, II, and VIc in addition to subunits IVI1 and Vb (33) under different pathophysiological conditions.…”

mentioning

confidence: 96%

Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes

Bansal

Srinivasan

Sadagopan

et al. 2012

Journal of Biological Chemistry

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Differential loss of cytochrome-coxidase subunits in ischemia-reperfusion injury: exacerbation of COI subunit loss by PKC-ε inhibition

Abstract: Yu Q, Nguyen T, Ogbi M, Caldwell RW, Johnson JA. Differential loss of cytochrome-c oxidase subunits in ischemia-reperfusion injury: exacerbation of COI subunit loss by PKC-ε inhibition.

Cited by 30 publications

References 60 publications

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

The subunit composition and function of mammalian cytochrome c oxidase

Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes

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