Helium postconditioning regulates expression of caveolin-1 and -3 and induces RISK pathway activation after ischaemia/reperfusion in cardiac tissue of rats.

Autor: Flick M; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany., Albrecht M; Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany., Oei GTML; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Steenstra R; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Kerindongo RP; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Zuurbier CJ; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Patel HH; Veterans Affairs San Diego Healthcare System and Department of Anaesthesiology, University of California, San Diego, 9500 Gilman Drive, 92093 La Jolla, California, USA., Hollmann MW; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Preckel B; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands., Weber NC; Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD Amsterdam, The Netherlands. Electronic address: N.C.Hauck@amc.uva.nl.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2016 Nov 15; Vol. 791, pp. 718-725. Date of Electronic Publication: 2016 Oct 11.
DOI: 10.1016/j.ejphar.2016.10.012
Abstrakt: Caveolae, lipid enriched invaginations of the plasma membrane, are epicentres of cellular signal transduction. The structural proteins of caveolae, caveolins, regulate effector pathways in anaesthetic-induced cardioprotection, including the RISK pathway. Helium (He) postconditioning (HePoc) is known to mimic anaesthetic conditioning and to prevent damage from myocardial infarction. We hypothesize that HePoc regulates caveolin-1 and caveolin-3 (Cav-1 and Cav-3) expression in the rat heart and activates the RISK pathway. Male Wistar rats (n=8, each group) were subjected to 25min of cardiac ischaemia followed by reperfusion (I/R) for 5, 15 or 30min (I/R 5/15/30). The HePoc groups underwent I/R with 70% helium ventilation during reperfusion (IR+He 5/15/30min). Sham animals received surgical treatment without I/R. After each protocol blood and hearts were retrieved. Tissue was obtained from the area-at-risk (AAR) and non-area-at-risk (NAAR) and processed for western blot analyses and reverse-transcription-real-time-polymerase-chain-reaction (RT-qPCR). Protein analyses revealed increased amounts of Cav-1 and Cav-3 in the membrane of I/R+He15 (AAR: Cav-1, P<0.05; Cav-3, P<0.05; both vs. I/R15). In serum, Cav-3 was found to be elevated in I/R+He15 (P<0.05 vs. I/R15). RT-qPCR showed increased expression of Cav-1 in IR+He15 in AAR tissue (P<0.05 vs. I/R15). Phosphorylation of RISK pathway proteins pERK1/2 (AAR: P<0.05 vs. I/R15) and pAKT (AAR: P<0.05; NAAR P<0.05; both vs. I/R15) was elevated in the cytosolic fraction of I/R+He15. These results suggest that 15min of HePoc regulates Cav-1 and Cav-3 and activates RISK pathway kinases ERK1/2 and AKT. These processes might be crucially involved in HePoc mediated cardioprotection.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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