The role of epsilon PKC in acute and chronic diseases: Possible pharmacological implications of its modulators. (September 2016)

• Record Type: Journal Article
• Authors: Capuani, Barbara; Pacifici, Francesca; Pastore, Donatella; Palmirotta, Raffaele; Donadel, Giulia; Arriga, Roberto; Bellia, Alfonso; Di Daniele, Nicola; Rogliani, Paola; Abete, Pasquale; Sbraccia, Paolo; Guadagni, Fiorella; Lauro, Davide; Della-Morte, David
• Is Part Of: Pharmacological research. Volume 111(2016:Sep.)
• Page Start: 659
• Page End: 667
• Publication Date: 2016-09
• Subjects: 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-aspartate -- MCAO middle cerebral artery occlusion -- TVO two vessel occlusion -- COX-2 cyclooxygenase-2 -- NAD+ nicotinamide adenine dinucleotide -- PDK1 phosphoinositide-dependent kinase -- TNF-α tumor necrosis factor alpha -- FFA free fatty acid -- NAFLD non alcoholic fatty liver disease -- PDK 1 phosphoinositide dependent kinase 1 -- ApoC3 apolipoprotein C3 -- RAF rapidly accelerated fibrosarcoma -- MEK mitogen activated protein kinase -- NF-κB the nuclear factor κB -- EGF epidermal growth factor -- Bcl-2B celllynphoma-2 -- Bax Bcl-2 associated protein -- BAD Bcl-2 antagonist of cell death -- CNV copy number variation -- EMT epithelial-mesenchymal transition -- CSC cancer stem cell -- mTOR mammalian target of rapamycin -- S6K ribomosal protein S6K; Epsilon PKC -- Epsilon PKC modulators -- Ischemic preconditioning -- Acute diseases -- Chronic diseases -- Metabolism -- Cancer; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.07.029
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: 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.