Chronic intermittent hypoxia affects the cytosolic phospholipase A(2)alpha/cyclooxygenase 2 pathway via beta(2)-adrenoceptor-mediated ERK/p38 stimulation

0466474 - FGÚ 2017 RIV US eng J - Journal Article
Míčová, P. - Hahnová, K. - Hlaváčková, Markéta - Elsnicová, B. - Chytilová, Anna - Holzerová, Kristýna - Žurmanová, J. - Neckář, Jan - Kolář, František - Nováková, Olga - Novotný, J.
Chronic intermittent hypoxia affects the cytosolic phospholipase A(2)alpha/cyclooxygenase 2 pathway via beta(2)-adrenoceptor-mediated ERK/p38 stimulation.
Molecular and Cellular Biochemistry. Roč. 423, 1-2 (2016), s. 151-163. ISSN 0300-8177. E-ISSN 1573-4919
R&D Projects: GA ČR(CZ) GA13-10267S
Institutional support: RVO:67985823
Keywords : heart * hypoxia * ischemia/reperfusion * phospholipase A2 * cyclooxygenase 2 * beta-adrenoceptor * MAPK
Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery
Impact factor: 2.669, year: 2016

Cardiac resistance against acute ischemia/reperfusion (I/R) injury can be enhanced by adaptation to chronic intermittent hypoxia (CIH), but the changes at the molecular level associated with this adaptation are still not fully explored. Phospholipase A(2) (PLA(2)) plays an important role in phospholipid metabolism and may contribute to membrane destruction under conditions of energy deprivation during I/R. The aim of this study was to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA(2)alpha (cPLA(2)alpha) and its phosphorylated form (p-cPLA(2)alpha), as well as other related signaling proteins in the left ventricular myocardium of adult male Wistar rats. Adaptation to CIH increased the total content of cPLA(2)alpha by 14 % in myocardial homogenate, and enhanced the association of p-cPLA(2)alpha with the nuclear membrane by 85 %. The total number of beta-adrenoceptors (beta-ARs) did not change but the beta(2)/beta(1) ratio markedly increased due to the elevation of beta(2)-ARs and drop in beta(1)-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and G(i)alpha proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E-2 (PGE(2)) increased by 36 and 84 %, respectively. In parallel, we detected increased phosphorylation of protein kinase C alpha, ERK1/2 and p38 (by 12, 48 and 19 %, respectively). These data suggest that adaptive changes induced in the myocardium by CIH may include activation of cPLA(2)alpha and COX-2 via beta(2)-AR/G(i)-mediated stimulation of the ERK/p38 pathway.
Permanent Link: http://hdl.handle.net/11104/0264754