Chronic intermittent hypoxia affects the cytosolic phospholipase A2α/cyclooxygenase 2 pathway via β2-adrenoceptor-mediated ERK/p38 stimulation.
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 A2(PLA2) 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 PLA2α (cPLA2α) and its phosphorylated form (p-cPLA2α), 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 cPLA2α by 14 % in myocardial homogenate, and enhanced the association of p-cPLA2α with the nuclear membrane by 85 %. The total number of β-adrenoceptors (β-ARs) did not change but the β2/β1ratio markedly increased due to the elevation of β2-ARs and drop in β1-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and Giα proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E2(PGE2) increased by 36 and 84 %, respectively. In parallel, we detected increased phosphorylation of protein kinase Cα, 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 cPLA2α and COX-2 via β2-AR/Gi-mediated stimulation of the ERK/p38 pathway.
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Petra
P
Micova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Klara
K
Hahnova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Marketa
M
Hlavackova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Barbara
B
Elsnicova
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Anna
A
Chytilova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Kristyna
K
Holzerova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Jitka
J
Zurmanova
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Jan
J
Neckar
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Frantisek
F
Kolar
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Olga
O
Novakova
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic. jiri.novotny@natur.cuni.cz.
Jiri
http://orcid.org/0000-0002-6372-0131
J
Novotny
D000818:Animals; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018343:Receptors, Adrenergic, beta-2; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D054513:Group IV Phospholipases A2
Cyclooxygenase 2; Heart; Hypoxia; Ischemia/reperfusion; MAPK; Phospholipase A2; β-Adrenoceptor
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