The role of epsilon PKC in acute and chronic diseases: Possible pharmacological implications of its modulators

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• 作者：Barbara Capuani^a ; Francesca Pacifici^a ; Donatella Pastore^a ; Raffaele Palmirotta^b ; Giulia Donadel^a ; Roberto Arriga^a ; Alfonso Bellia^a ; Nicola Di Daniele^a ; Paola Rogliani^a ; Pasquale Abete^c ; Paolo Sbraccia^a ; Fiorella Guadagni^d ; ^e ; Davide Lauro^a ; David Della-Morte ; PhD^a ; ^d ; ^{david.dellamorte@uniroma2.it" class="auth_mail" title="E-mail the corresponding author} (MD)
• 关键词：PKC ; protein kinase C ; IPC ; ischemic pre conditioning ; RACK ; receptor for activated C-kinase ; DAG ; diacylglycerol ; beta COP ; coatomer subunit beta ; CHOK1 ; chinese hamster ovary K1 ; CVD ; cardiovascular disease ; mKATP ; ATP-sensitive mitochondrial potassium channels ; VSMC ; vascular smooth muscle cell ; CPK ; creatinine phosphokinase ; PI3-K ; phosphatidylinositol-3-kinase ; OGD ; oxygen glucose deprivation ; ERK ; extracellular signal-regulated kinase ; A1AR ; adenosine A1 receptors ; NMDA ; N-methyl-d-asparta
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：111
• 期：Complete
• 页码：659-667
• 全文大小：1327 K

文摘

Epsilon Protein kinase C (εPCK) is a particular kinase that, when activated, is able to protect against different stress injuries and therefore has been proposed to be a potential molecular target against acute and chronic diseases. Particular attention has been focused on εPCK for its involvement in the protective mechanism of Ischemic Preconditioning (IPC), a powerful endogenous mechanism characterized by subthreshold ischemic insults able to protect organs against ischemic injury. Therefore, in the past decades several εPCK modulators have been tested with the object to emulate εPCK mediate protection. Among these the most promising, so far, has been the ΨεRACK peptide, a homologous of RACK receptor for εPKC, that when administrated can mimic its effect in the cells. However, results from studies on εPCK indicate controversial role of this kinase in different organs and diseases, such as myocardial infarct, stroke, diabetes and cancer. Therefore, in this review we provide a discussion on the function of εPCK in acute and chronic diseases and how the different activators and inhibitors have been used to modulate its activity. A better understanding of its function is still needed to definitively target εPCK as novel therapeutic strategy.