Antioxidant tempol suppresses heart cytosolic phospholipase A 2 α 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 A2 (PLA2 s) 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 PLA2 (cPLA2 α), its phosphorylated form (p-cPLA2 α), calcium-independent (iPLA2 ), and secretory (sPLA2 IIA) 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 PLA2 s expression and phospholipid FA remodeling. While CIH did not affect PLA2 s mRNA levels, it increased the total cPLA2 α protein in cytosol and membranes (by 191% and 38%, respectively) and p-cPLA2 α (by 23%) in membranes. On the contrary, both iPLA2 and sPLA2 IIA 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 cPLA2 α up-regulation and its phosphorylation on Ser505 . Our results show that CIH diversely affect myocardial PLA2 s and suggest that ROS are responsible for the activation of cPLA2 α under these conditions.