TY - JOUR
T1 - Helium postconditioning regulates expression of caveolin-1 and -3 and induces RISK pathway activation after ischaemia/reperfusion in cardiac tissue of rats
AU - Flick, Moritz
AU - Albrecht, Martin
AU - Oei, Gezina T. M. L.
AU - Steenstra, Renske
AU - Kerindongo, Raphaela P.
AU - Zuurbier, Coert J.
AU - Patel, Hemal H.
AU - Hollmann, Markus W.
AU - Preckel, Benedikt
AU - Weber, Nina C.
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.ejphar.2016.10.012
DO - https://doi.org/10.1016/j.ejphar.2016.10.012
M3 - Article
C2 - 27742593
SN - 0014-2999
VL - 791
SP - 718
EP - 725
JO - European journal of pharmacology
JF - European journal of pharmacology
ER -