Chronic intermittent hypoxia affects the cytosolic phospholipase A2α/cyclooxygenase 2 pathway via β2-adrenoceptor-mediated ERK/p38 stimulation
Abstrakt
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)α (cPLA(2)α) and its phosphorylated form (p-cPLA(2)α), 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)α by 14 % in myocardial homogenate, and enhanced the association of p-cPLA(2)α with the nuclear membrane by 85 %.
The total number of β-adrenoceptors (β-ARs) did not change but the β(2)/β(1) ratio markedly increased due to the elevation of β(2)-ARs and drop in β(1)-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and G(i)α 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 α, 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)α and COX-2 via β(2)-AR/G(i)-mediated stimulation of the ERK/p38 pathway.