Protein Kinase C- ξ is Responsible for the Protection of Preconditioning in Rabbit Cardiomyocytes

Liu, Guang S.; Cohen, Michael V.; Mochly‐Rosen, Daria; Downey, James M.

doi:10.1006/jmcc.1999.1026

Cited by 239 publications

(186 citation statements)

References 29 publications

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“…Preliminary data suggested that EETs might only partially activate [31] the mito K ATP channel and could be working synergistically with other cardioprotective sites, such as the sarc K ATP channel or the mito K Ca channel. Additional evidence has demonstrated an important role for PKA and PKC in the cardioprotective pathway involving K + channels [79,80,81]. Further experiments will help determine if EET-mediated cardioprotection involves early activation or co-localization of PKA or PKC to the mitochondria.…”

Section: Cardioprotective Signaling Pathwaysmentioning

confidence: 97%

Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury

Seubert¹,

Zeldin²,

Nithipatikom³

et al. 2007

Prostaglandins & Other Lipid Mediators

134

131

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Cardiomyocyte injury following ischemia-reperfusion can lead to cell death and result in cardiac dysfunction. A wide range of cardioprotective factors have been studied to date, but only recently has the cardioprotective role of fatty acids, specifically arachidonic acid (AA), been investigated. This fatty acid can be found in the membranes of cells in an inactive state and can be released by phospholipases in response to several stimuli, such as ischemia. The metabolism of AA involves the cycloxygenase (COX) and lipoxygenase (LOX) pathways, as well as the less well characterized cytochrome P450 (CYP) monooxygenase pathway. Current research suggests important differences with respect to the cardiovascular actions of specific CYP mediated arachidonic acid metabolites. For example, CYP mediated hydroxylation of AA produces 20-hydroxyeicosatetraenoic acid (20-HETE) which has detrimental effects in the heart during ischemia, pro-inflammatory effects during reperfusion and potent vasoconstrictor effects in the coronary circulation. Conversely, epoxidation of AA by CYP enzymes generates 5,6-, 8,9-, 11,12-and 14,15-epoxyeicosatrienoic acids (EETs) that have been shown to reduce ischemia-reperfusion injury, have potent anti-inflammatory effects within the vasculature, and are potent vasodilators in the coronary circulation. This review aims to provide an overview of current data on the role of these CYP pathways in the heart with an emphasis on their involvement as mediators of ischemia-reperfusion injury. A better understanding of these relationships will facilitate identification of novel targets for the prevention and/or treatment of ischemic heart disease, a major worldwide public health problem.

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Section: Cardioprotective Signaling Pathwaysmentioning

confidence: 97%

Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury

Seubert¹,

Zeldin²,

Nithipatikom³

et al. 2007

Prostaglandins & Other Lipid Mediators

134

131

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“…Similarly, peptide translocation inhibitors inhibit the translocation and function of PKC in an isozyme-selective manner (Aley et al, 2000;Chen and Mochly-Rosen, 2001;Gray et al, 1997;Hu et al, 2000;Hundle et al, 1997;Johnson et al, 1996a;Liu et al, 1999;Mayne and Murray, 1998;Mochly-Rosen et al, 2000;Yedovitzky et al, 1997;Zhang et al, 1997 (see below)). …”

Section: Modulation Of Binding To Adaptor Proteinsð a Therapeutic Oppmentioning

confidence: 99%

Adaptor proteins in protein kinase C-mediated signal transduction

2001

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Spatial and temporal organization of signal transduction is essential in determining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrates and away from others in order to optimize precision and speed of response. Here, we describe the role of adaptor proteins in determining the speci®c function of individual protein kinase C (PKC) isozymes. These isozymeselective proteins were called collectively RACKs (receptors for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-speci®c inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACKs anchor other signaling enzymes. RACK1, the anchoring protein for activated bIIPKC, binds for example, Src tyrosine kinase, integrin, and phosphodiesterase. RACK2, the ePKC-speci®c RACK, is a coated-vesicle protein and thus is involved in vesicular release and cell ± cell communication. Therefore, RACKs are not only adaptors for PKC, but also serve as adaptor proteins for several other signaling enzymes. Because at least some of the proteins that bind to RACKs, including PKC itself, regulate cell growth, modulating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identi®cation of novel therapeutic targets. Oncogene (2001) 20, 6339 ± 6347.

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“…A Tat-carrier peptide control and PKC isoenzyme-selective translocation inhibitors directed against the classical PKC isoenzymes [2, 37,48,49] were also tested. Following hypoxia, particulate cell fractions were isolated and subjected to the in vitro phosphorylation reactions.…”

Section: Introduction Of a Pkcε-selective Translocation Inhibitor Intmentioning

confidence: 99%

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

Ogbi

Johnson

2005

Biochemical Journal

117

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We have previously identified a phorbol ester-induced PKCϵ (protein kinase Cϵ) interaction with the (∼18 kDa) COIV [CO (cytochrome c oxidase) subunit IV] in NCMs (neonatal cardiac myocytes). Since PKCϵ has been implicated as a key mediator of cardiac PC (preconditioning), we examined whether hypoxic PC could induce PKCϵ–COIV interactions. Similar to our recent study with phorbol esters [Ogbi, Chew, Pohl, Stuchlik, Ogbi and Johnson (2004) Biochem. J. 382, 923–932], we observed a time-dependent increase in the in vitro phosphorylation of an approx. 18 kDa protein in particulate cell fractions isolated from NCMs subjected to 1–60 min of hypoxia. Introduction of a PKCϵ-selective translocation inhibitor into cells attenuated this in vitro phosphorylation. Furthermore, when mitochondria isolated from NCMs exposed to 30 min of hypoxia were subjected to immunoprecipitation analyses using PKCϵ-selective antisera, we observed an 11.1-fold increase in PKCϵ–COIV co-precipitation. In addition, we observed up to 4-fold increases in CO activity after brief NCM hypoxia exposures that were also attenuated by introducing a PKCϵ-selective translocation inhibitor into the cells. Finally, in Western-blot analyses, we observed a >2-fold PC-induced protection of COIV levels after 9 h index hypoxia. Our studies suggest that a PKCϵ–COIV interaction and an enhancement of CO activity occur in NCM hypoxic PC. We therefore propose novel mechanisms of PKCϵ-mediated PC involving enhanced energetics, decreased mitochondrial reactive oxygen species production and the preservation of COIV levels.

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Protein Kinase C- ξ is Responsible for the Protection of Preconditioning in Rabbit Cardiomyocytes

Cited by 239 publications

References 29 publications

Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury

Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury

Adaptor proteins in protein kinase C-mediated signal transduction

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

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