Chronic intermittent hypoxia affects the cytosolic phospholipase A₂α/cyclooxygenase 2 pathway via β₂-adrenoceptor-mediated ERK/p38 stimulation

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 A₂ (PLA₂) 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 PLA₂α (cPLA₂α) and its phosphorylated form (p-cPLA₂α), 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 cPLA₂α by 14 % in myocardial homogenate, and enhanced the association of p-cPLA₂α with the nuclear membrane by 85 %. The total number of β-adrenoceptors (β-ARs) did not change but the β₂/β₁ ratio markedly increased due to the elevation of β₂-ARs and drop in β₁-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and G_iα proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E₂ (PGE₂) increased by 36 and 84 %, respectively. In parallel, we detected increased phosphorylation of protein kinase Cα, 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 cPLA₂α and COX-2 via β₂-AR/G_i-mediated stimulation of the ERK/p38 pathway.