Micova Petra, Hahnova Klara, Hlavackova Marketa, Elsnicova Barbara, Chytilova Anna, Holzerova Kristyna, Zurmanova Jitka, Neckar Jan, Kolar Frantisek, Novakova Olga, Novotny Jiri
Department of Physiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Mol Cell Biochem. 2016 Dec;423(1-2):151-163. doi: 10.1007/s11010-016-2833-8. Epub 2016 Sep 30.
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 A (PLA) 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 PLAα (cPLAα) and its phosphorylated form (p-cPLAα), 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 cPLAα by 14 % in myocardial homogenate, and enhanced the association of p-cPLAα with the nuclear membrane by 85 %. The total number of β-adrenoceptors (β-ARs) did not change but the β/β ratio markedly increased due to the elevation of β-ARs and drop in β-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and Gα proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E (PGE) 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 cPLAα and COX-2 via β-AR/G-mediated stimulation of the ERK/p38 pathway.
对慢性间歇性缺氧（CIH）的适应可增强心脏对急性缺血/再灌注（I/R）损伤的抵抗力，但与这种适应相关的分子水平变化仍未得到充分研究。磷脂酶A（PLA）在磷脂代谢中起重要作用，可能在I/R期间能量剥夺条件下导致膜破坏。本研究的目的是确定CIH（7000米，每天8小时，共5周）对成年雄性Wistar大鼠左心室心肌中胞质型PLAα（cPLAα）及其磷酸化形式（p-cPLAα）以及其他相关信号蛋白表达的影响。对CIH的适应使心肌匀浆中cPLAα的总含量增加了14%，并使p-cPLAα与核膜的结合增加了85%。β-肾上腺素能受体（β-ARs）的总数没有变化，但由于β-ARs升高和β-ARs下降，β/β比值显著增加。同时，腺苷酸环化酶的量减少了49%，Gα蛋白增加了约50%。除此之外，环氧合酶2（COX-2）和前列腺素E（PGE）分别增加了36%和84%。同时，我们检测到蛋白激酶Cα、ERK1/2和p38的磷酸化增加（分别增加了12%、48%和19%）。这些数据表明，CIH在心肌中诱导的适应性变化可能包括通过β-AR/G介导的ERK/p38途径刺激激活cPLAα和COX-2。
