Protein kinase C-dependent activation of KATP channel enhances adenosine-induced cardioprotection.
Protein kinase C-dependent activation of KATP channel enhances adenosine-induced cardioprotection.
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KATP 通道的蛋白激酶 C 依赖性激活可增强腺苷诱导的心脏保护作用。
DOI：
10.1042/bj3360337
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Liang,BT
中科院分区：
文献类型：
--
作者：
Liang,BT
蛋白激酶C(PKC)的预先激活可以使心肌细胞在随后的缺血中免受损伤。本研究利用体外培养的鸡心室肌细胞模拟缺血和预适应模型，探讨了PKC介导的预适应的生化机制。在随后的90分钟缺血期间，暴露于PMA 5分钟增强了吡那地尔介导心脏保护的能力，这与PKC启动的KATP通道的持续激活一致。先前短暂接触PMA也与腺苷A1或A3受体激动剂2-氯-N6-环戊基腺苷orN6-(3-iodobenzyl)adenosine-5´-N-methyluronamide在随后的缺血期间诱导心脏保护反应的能力增强有关。在用PMA预处理的心肌细胞中，KATP通道拮抗剂格列本脲或5-羟基癸酸可阻断受体激动剂介导的心肌保护作用。因此，KATP通道在腺苷A1和A3受体的下游起作用，介导先前PMA暴露所产生的保护作用。腺苷受体介导的效应与KATP通道激活有关。PMA处理不影响A1或A3受体介导的其他效应，如对腺苷环化酶的抑制，排除了PMA直接刺激受体或G蛋白的可能性。目前的结果表明，预先刺激PKC导致持续的KATP通道激活，这反过来使心肌细胞对随后的缺血时腺苷A1和A3受体激动剂的保护作用更有反应。
Prior activation of protein kinase C (PKC) can precondition the cardiac cell against injury during subsequent ischaemia. By using cultured chick ventricular cell model for simulated ischaemia and preconditioning, the present study investigated the biochemical mechanism underlying the PKC-mediated preconditioning. A 5 min exposure to PMA enhanced the ability of pinacidil to mediate cardioprotection during a subsequent 90 min period of ischaemia, which is consistent with a sustained activation of the KATPchannel initiated by PKC. The brief prior exposure to PMA was also associated with an enhanced ability of the adenosine A1or A3receptor agonist 2-chloro-N6-cyclopentyladenosine orN6-(3-iodobenzyl)adenosine-5´-N-methyluronamide to elicit a cardioprotective response during the subsequent ischaemia. In myocytes pretreated with PMA, the cardioprotection mediated by receptor agonist was blocked by the concomitant presence of KATP-channel antagonists glibenclamide or 5-hydroxydecanoic acid during the ischaemia. Thus the KATPchannel acts downstream of the adenosine A1and A3receptors in mediating the protective effect due to prior PMA exposure. KATPchannel activation is responsible for the adenosine receptor-mediated effect. PMA treatment had no effect on other A1or A3receptor-mediated effects such as the inhibition of adenylate cyclase, ruling out a direct stimulation of the receptor or G-protein by PMA. The present results indicate that prior stimulation of PKC causes a sustained KATPchannel activation, which in turn renders the myocyte more responsive to the protective action of adenosine A1and A3receptor agonists during the subsequent ischaemia.