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短暂低氧/复氧对培养新生兔心肌细胞丝裂素活化蛋白激酶活性的影响

于文杰, 姚兴海, 刘秀华, 陈魁, 牛大地, 苏静怡, 唐朝枢

北京医科大学心血管基础研究所. 北京 100083

摘要

心肌细胞短暂低氧可诱导对后续长时间低氧所致细胞严重损伤的耐力增强，已在心脏预处理(PC)模型上得到证实，但PC发生的细胞内信号传导途径目前尚不清楚。作者在培养的新生兔心肌细胞低氧/复氧模型上，观察丝裂素活化蛋白激酶(MAPK)和核蛋白体S6激酶(S6K)活性改变。结果发现：低氧60min后、复氧15min，细胞总MAPK和核MAPK活性分别较对照组增加95％和230％(P＜0.01)；S6K活性在复氧30min轻对照组增高142％(P＜0.01)。应用磷酸酯酶1(Ppase1)抑制剂ocadaic acid(OA，1μmol/L)，可加强低氧/复氧引起MAPK和S6K激活，而酪氨酸激酶(TyrK)阻断剂(genistein)，蛋白激酶C(PKC)阻断剂(H_(7))和预先用PKC激动剂(PMA)孵育使细胞PKC下调，都减轻了低氧诱导的MAPK和S6K的激活。蛋白激酶A(PKA)抑制剂(H_(89))、钙调素依赖蛋白激酶(PKM)抑制剂(W_(7))和PPase2a抑制剂(OA，10nmol/L)却无影响。结果表明，心肌细胞短暂低氧/复氧激活了MAPK和S6K激活过程为PKC，TyrK和PPasel所参与，似未涉及PKA，PKM和PPase2a。

关键词： 心肌细胞; 低氧/复氧; 丝裂素活化蛋白激酶; 核蛋白体S6激酶

Effects of hypoxia/reoxygenation on mitogen-activated protein kinase activity in cultured neonatal rabbit cardiac myocytes

Yu Wenjie, Yao Xinghai, Liu Xiuhua, Chen Kui, Niu Dadi, Su Jingyi, Tang Chaoshu

Institute of Cardiovascular Research, Beijing Medical University. Beijing 100083, China

Abstract

Cardiomyocytes subjected to brief episode of hypoxia possess a resistance to serious damaging effect exerted by a subsequent long-time hypoxia on these cells, which is called hypoxic preconditioning (PC). The pathway 0f intracellular signal transduction during hypoxia PC has not yet been validated. On a model of hypoxia/ reoxygenation (H/R) of cultured neonatal rabbit cardiomyocytes, the present study is taken to investigate the changes of mitogenactivated protein kinase (MAPK) and ribosomal S6 kinase (S6K) activity. It was found that intracellular total MAPK and nuclear MAPK, afer a 15-min period of reoxygenation preceded by a single 60-min period of hypoxia, were increased by 95% and 230%, respectively. Intracellulax S6K activity increased by 142% at 30 min of H/R vs the control group (P<0.01). Phosphatase 1 (PPase 1) inhibitor (ocadaic acid, OA 1#mu#mol/L) augmented the increase of MAPK and S6K activity induced hy H/R.

Key words: Cardiomyocytes;Hypoxia/reoxygenation;Mitogen-activated kinase;Ribosomal S6 kinase

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引用本文：

于文杰, 姚兴海, 刘秀华, 陈魁, 牛大地, 苏静怡, 唐朝枢. 短暂低氧/复氧对培养新生兔心肌细胞丝裂素活化蛋白激酶活性的影响[J]. 生理学报 1997; 49 (5): .

Yu Wenjie, Yao Xinghai, Liu Xiuhua, Chen Kui, Niu Dadi, Su Jingyi, Tang Chaoshu. Effects of hypoxia/reoxygenation on mitogen-activated protein kinase activity in cultured neonatal rabbit cardiac myocytes. Acta Physiol Sin 1997; 49 (5): (in Chinese with English abstract).