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Chronic intermittent hypoxia affects the cytosolic phospholipase A2α/cyclooxygenase 2 pathway via β2-adrenoceptor-mediated ERK/p38 stimulation

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Abstract

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/β1 ratio 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.

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Acknowledgments

This work was supported by the Charles University Grant Agency (392615), the Czech Science Foundation (13-10267S), the Ministry of Education, Youth and Sport of the Czech Republic (SVV-260313/2016) and the Operational Program OP VaVpI (CZ.1.05/4.1.00/16.0347).

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  1. Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic

    Petra Micova, Klara Hahnova, Marketa Hlavackova, Barbara Elsnicova, Kristyna Holzerova, Jitka Zurmanova, Olga Novakova & Jiri Novotny

  2. Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic

    Marketa Hlavackova, Anna Chytilova, Kristyna Holzerova, Jan Neckar, Frantisek Kolar & Olga Novakova

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  1. Petra Micova
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Micova, P., Hahnova, K., Hlavackova, M. et al. Chronic intermittent hypoxia affects the cytosolic phospholipase A2α/cyclooxygenase 2 pathway via β2-adrenoceptor-mediated ERK/p38 stimulation. Mol Cell Biochem 423, 151–163 (2016). https://doi.org/10.1007/s11010-016-2833-8

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