Antioxidant tempol suppresses heart cytosolic phospholipase A(2)alpha stimulated by chronic intermittent hypoxia

0477749 - FGÚ 2018 RIV CA eng J - Článek v odborném periodiku
Míčová, P. - Klevstig, Martina - Holzerová, Kristýna - Vecka, M. - Žurmanová, J. - Neckář, Jan - Kolář, František - Nováková, Olga - Novotný, J. - Hlaváčková, Markéta
Antioxidant tempol suppresses heart cytosolic phospholipase A(2)alpha stimulated by chronic intermittent hypoxia.
Canadian Journal of Physiology and Pharmacology. Roč. 95, č. 8 (2017), s. 920-927. ISSN 0008-4212. E-ISSN 1205-7541
Grant CEP: GA ČR(CZ) GJ16-12420Y; GA ČR(CZ) GA13-10267S
Institucionální podpora: RVO:67985823
Klíčová slova: heart * chronic intermittent hypoxia * oxidative stress * phospholipases A(2) * tempol
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 2.210, rok: 2017

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 (PLA2s) 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(2) (cPLA(2)alpha), its phosphorylated form (p-cPLA(2)alpha), calcium-independent (iPLA2), and secretory (sPLA2IIA) 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 PLA2s expression and phospholipid FA remodeling. While CIH did not affect PLA2s mRNA levels, it increased the total cPLA(2)alpha protein in cytosol and membranes (by 191% and 38%, respectively) and p-cPLA(2)alpha (by 23%) in membranes. Onthe contrary, both iPLA2 and sPLA2IIA 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(2)alpha up-regulation and its phosphorylation on Ser505. Our results show that CIH diversely affect myocardial PLA2s and suggest that ROS are responsible for the activation of cPLA(2)alpha under these conditions.
Trvalý link: http://hdl.handle.net/11104/0273989