| Catestatin reduces myocardial ischaemia/reperfusion injury: involvement of PI3K/Akt, PKCs, mitochondrial K(ATP) channels and ROS signalling. | |
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MedLine Citation:
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PMID: 23319164 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Catestatin (CST) limits myocardial ischaemia/reperfusion (I/R) injury with unknown mechanisms. Clearly phosphoinositide-3-kinase (PI3K), protein kinase C (PKC) isoforms, including intra-mitochondrial PKCε, mitochondrial K(ATP) (mitoK(ATP)) channels and subsequent reactive oxygen species (ROS)-signalling play important roles in postconditioning cardioprotection, preventing mitochondrial permeability transition pore (mPTP) opening. Therefore, we studied the role of these extra- and intra-mitochondrial factors in CST-induced protection. Isolated rat hearts and H9c2 cells underwent I/R and oxidative stress, respectively. In isolated hearts CST (75nM, CST-Post) given in early-reperfusion significantly reduced infarct size, limited post-ischaemic contracture, and improved recovery of developed left ventricular pressure. PI3K inhibitor, LY-294002 (LY), large spectrum PKC inhibitor, Chelerythrine (CHE), specific PKCε inhibitor (εV1-2), mitoK(ATP) channel blocker, 5-Hydroxydecanoate (5HD) or ROS scavenger, 2-mercaptopropionylglycine (MPG) abolished the infarct-sparing effect of CST. Notably the CST-induced contracture limitation was maintained during co-infusion of 5HD, MPG or εV1-2, but it was lost during co-infusion of LY or CHE. In H9c2 cells challenged with H(2)O(2), mitochondrial depolarization (an index of mPTP opening studied with JC1-probe) was drastically limited by CST (75nM). Our results suggest that the protective signalling pathway activated by CST includes mitoK(ATP) channels, ROS signalling and prevention of mPTP opening, with a central role for upstream PI3K/Akt and PKCs. In fact, all inhibitors completely abolished CST-infarct-sparing effect. Since CST-anti-contracture effect cannot be explained by intra-mitochondrial mechanisms (PKCε activation and mitoK(ATP) channel opening) or ROS signalling, it is proposed that these downstream signals are part of a reverberant loop which re-activates upstream PKCs, which therefore play a pivotal role in CST-induced protection. |
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Authors:
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Maria-Giulia Perrelli; Francesca Tullio; Carmelina Angotti; Maria Carmela Cerra; Tommaso Angelone; Bruno Tota; Giuseppe Alloatti; Claudia Penna; Pasquale Pagliaro |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-15 |
Journal Detail:
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Title: Pflugers Archiv : European journal of physiology Volume: - ISSN: 1432-2013 ISO Abbreviation: Pflugers Arch. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical and Biological Sciences, University of Torino, Orbassano, Turin, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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