Protein kinase Cϵ interacts with cytochrome <i>c</i> oxidase subunit IV and enhances cytochrome <i>c</i> oxidase activity in neonatal cardiac myocyte preconditioning

Ogbi, Mourad; Johnson, John A.

doi:10.1042/bj20050757

Cited by 97 publications

(123 citation statements)

References 75 publications

(133 reference statements)

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“…Mitochondria have been implicated in these protective pathways due to their role in ATP synthesis and maintenance of Ca 2+ homeostasis. The PKC-δ and -ε isoforms interact specifically with mitochondria (Majumder et al, 2000;McCarthy et al, 2005;Ogbi and Johnson, 2006). IPC protection may be created by a transient increase in the concentration of Ca 2+ in the mitochondria, which increases the activity of pyruvate dehydrogenase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase-3, enzymes key to the ATP synthesis pathway.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C subtypes and retinal ischemic preconditioning

Dreixler

Shaikh

Shenoy

et al. 2008

Experimental Eye Research

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The purpose of our study was to determine the specific subtypes of protein kinase C involved in the neuroprotection afforded by retinal ischemic preconditioning (IPC), their relationship to the opening of mitochondrial KATP (mKATP) channels, and their role in apoptosis after preconditioning and ischemia. Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. Using immunohistochemistry and image analysis, we determined cellular localization of PKC subtypes. We blocked PKC-δ and -ε to study the effect on protection with IPC or with IPC-mimicking by the opening of mKATP channels. PKC subtypes were inhibited pharmacologically or with interfering RNA. Electroretinography assessed functional recovery after ischemia. IPC was effectively mimicked by injection of diazoxide to open the mKATP channel. IPC and/or its mimicking were attenuated by the PKC-δ inhibitor rottlerin and by interfering RNA targeting PKC-δ or -ε. Using TUNEL staining and Western blotting for caspase-3 and fodrin breakdown we assessed apoptosis. The injection of interfering RNA to PKC-δ and -ε before preconditioning significantly enhanced TUNEL staining as well as the cleavage of caspase-3 and fodrin after ischemia. In summary, our experiments have shown that both PKC-δ and -ε subtypes are involved in the cellular signaling that results in neuroprotection from IPC and that both are downstream of the opening of mKATP channels.

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Section: Discussionmentioning

confidence: 99%

Protein kinase C subtypes and retinal ischemic preconditioning

Dreixler

Shaikh

Shenoy

et al. 2008

Experimental Eye Research

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“…It also serves as a direct sensor of the oxygen levels available in the cell and nitric oxide (NO) competes with binding of oxygen to CytCox [49]. It has been shown in studies using cardiac myocytes that PKCε, when activated by hypoxia, interacts with subunit IV (COIV), increasing the activity of CytCox [50]. This presumably increases respiration and energetics and protects the cell from ROS caused by electron leakage at complex I and III.…”

Section: If This Proves To Be the Case What Proteins Is Pkcε Bindingmentioning

confidence: 99%

Protein kinase C as a stress sensor

Barnett

Madgwick

Takemoto

2007

Cellular Signalling

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While there are many reviews which examine the group of proteins known as protein kinase C (PKC), the focus of this article is to examine the cellular roles of two PKCs that are important for stress responses in neurological tissues (PKCγ and ε) and in cardiac tissues (PKCε). These two kinases, in particular, seem to have overlapping functions and interact with an identical target, connexin 43 (Cx43), a gap junction protein which is central to proper control of signals in both tissues. While PKCγ and PKCε both help protect neural tissue from ischemia, PKCε is the primary PKC isoform responsible for responding to decreased oxygen, or ischemia, in the heart. Both do this through Cx43.It is clear that both PKCγ and PKCε are necessary for protection from ischemia. However, the importance of these kinases has been inferred from preconditioning experiments which demonstrate that brief periods of hypoxia protect neurological and cardiac tissues from future insults, and that this depends on the activation, translocation, or ability for PKCγ and/or PKCε to interact with distinct cellular targets, especially Cx43.This review summarizes the recent findings which define the roles of PKCγ and PKCε in cardiac and neurological functions and their relationships to ischemia/reperfusion injury. In addition, a biochemical comparison of PKC γ and PKC ε and a proposed argument for why both forms are present in neurological tissue while only PKC ε is present in heart, are discussed. Finally, the biochemistry of PKCs and future directions for the field are discussed, in light of this new information.

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“…In contrast, several reports demonstrate that in heart tissue, PKCε is activated by both TPA and hypoxic conditions, and that upon activation, this isoform translocates to distinct cellular locations such as to mitochondria (Ogbi and Johnson, 2006). To determine if PKCε is activated by hypoxia in lens epithelial cells, N/N1003A cells were incubated in either normoxic (21% oxygen) or hypoxic (5% oxygen) conditions for 12 hr.…”

Section: Lens Pkc ε Is Activated By Hypoxiamentioning

confidence: 99%

“…PKCε plays an anti-apoptotic role in these instances and seems to be compensating for energy deficits and apoptotic signals encountered during hypoxia (Baines, 2002). During cardiac ischemia PKCε also associates with mitochondrial cytochrome C oxidase IV (CytCOx) resulting in activation of the CytCOx (Ogbi and Johnson, 2006). PKCε is widely expressed in the heart and neural tissue, including retina and lens (Berthoud, et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C epsilon activates lens mitochondrial cytochrome c oxidase subunit IV during hypoxia

Barnett

Lin

Akoyev

et al. 2008

Experimental Eye Research

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Protein Kinase C (PKC) isoforms have been identified as major cellular signaling proteins that act directly in response to oxidation conditions. In retina and lens two isoforms of PKC respond to changes in oxidative stress, PKCγ and PKCε, while only PKCε is found in heart. In heart the PKCε acts on connexin 43 to protect from hypoxia. The presence of both isoforms in the lens led to this study to determine if lens PKCε had unique targets. Both lens epithelial cells in culture and whole mouse lens were examined using PKC isoform-specific enzyme activity assays, coimmunoprecipitation, confocal microscopy, immunoblots, and light and electron microscopy. PKCε was found in lens epithelium and cortex but not in the nucleus of mouse lens. The PKCε isoform was activated in both epithelium and whole lens by 5% oxygen when compared to activity at 21% oxygen. In hypoxic conditions (5% oxygen) the PKCε co-immunoprecipitated with the mitochondrial cytochrome C oxidase IV subunit (CytCOx). Concomitant with this the CytCOx enzyme activity was elevated and increased co-localization of CytCOx with PCKε was observed using immunolabeling and confocal microscopy. In contrast, no hypoxia-induced activation of CytCOx was observed in lenses from the PKCε knockout mice. Lens from 6 week old PKCε knockout mice had a disorganized bow region which was filled with vacuoles indicating a possible loss of mitochondria but the size of the lens was not altered. Electron microscopy demonstrated that the nuclei of the PCKε knockout mice were abnormal in shape. Thus, PKCε is found to be activated by hypoxia and this results in the activation of the mitochondrial protein CytCOx. This could protect the lens from mitochondrial damage under the naturally hypoxic conditions observed in this tissue. Lens oxygen levels must remain low. Elevation of oxygen which occurs during vitreal detachment or liquification is associated with cataracts. We hypothesize that elevated oxygen could cause inhibition of PKCε resulting in a loss of mitochondrial protection.

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Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

Cited by 97 publications

References 75 publications

Protein kinase C subtypes and retinal ischemic preconditioning

Protein kinase C subtypes and retinal ischemic preconditioning

Protein kinase C as a stress sensor

Protein kinase C epsilon activates lens mitochondrial cytochrome c oxidase subunit IV during hypoxia

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