Antioxidant tempol suppresses heart cytosolic phospholipase A 2 α stimulated by chronic intermittent hypoxia

• Published in: Canadian journal of physiology and pharmacology 2017-08, Vol.95 (8), p.920-927
• Main Authors: Míčová, Petra, Klevstig, Martina, Holzerová, Kristýna, Vecka, Marek, Žurmanová, Jitka, Neckář, Jan, Kolář, František, Nováková, Olga, Novotný, Jiří, Hlaváčková, Markéta
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Chronic Disease; Cyclic N-Oxides - pharmacology; Fatty Acids - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Group IV Phospholipases A2 - genetics; Group IV Phospholipases A2 - metabolism; Hypoxia - enzymology; Hypoxia - metabolism; Male; Phosphorylation - drug effects; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Spin Labels
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0022

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 (PLA 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 PLA (cPLA α), its phosphorylated form (p-cPLA α), calcium-independent (iPLA ), and secretory (sPLA 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 PLA s expression and phospholipid FA remodeling. While CIH did not affect PLA s mRNA levels, it increased the total cPLA α protein in cytosol and membranes (by 191% and 38%, respectively) and p-cPLA α (by 23%) in membranes. On the contrary, both iPLA and sPLA 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 cPLA α up-regulation and its phosphorylation on Ser . Our results show that CIH diversely affect myocardial PLA s and suggest that ROS are responsible for the activation of cPLA α under these conditions.