Antioxidant tempol suppresses heart cytosolic phospholipase Aα stimulated by chronic intermittent hypoxia.

Adaptation to chronic intermittent hypoxia (CIH) is associated with reactive oxygen species (ROS) generation implicated in the improved cardiac tolerance against acute ischemia-reperfusion injury. Phospholipases A (PLAs) play an important role in cardiomyocyte phospholipid metabolism influencing membrane homeostasis. Here we aimed to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA (cPLAα), its phosphorylated form (p-cPLAα), calcium-independent (iPLA), and secretory (sPLAIIA) at protein and mRNA levels, as well as fatty acids (FA) profile in left ventricular myocardium of adult male Wistar rats. Chronic administration of antioxidant tempol was used to verify the ROS involvement in CIH effect on PLAs expression and phospholipid FA remodeling. While CIH did not affect PLAs mRNA levels, it increased the total cPLAα protein in cytosol and membranes (by 191% and 38%, respectively) and p-cPLAα (by 23%) in membranes. On the contrary, both iPLA and sPLAIIA were downregulated by CIH. CIH further decreased phospholipid n-6 polyunsaturated FA (PUFA) and increased n-3 PUFA proportion. Tempol treatment prevented only CIH-induced cPLAα up-regulation and its phosphorylation on Ser. Our results show that CIH diversely affect myocardial PLAs and suggest that ROS are responsible for the activation of cPLAα under these conditions.