Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischernia and reperfusion
Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischernia and reperfusion
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DOI：
10.1016/j.febslet.2004.03.120
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发表时间：
2004-05-21
期刊：
影响因子：
3.5
通讯作者：
Abe, J
中科院分区：
文献类型：
--
作者：
Cameron, SJ;Itoh, S;Abe, J
大 MAP 激酶 1 (BMK1/ERK5) 在心血管系统的产前发育和产后心脏偏心肥大中发挥着关键作用。在已知存在的 MAPK 激酶 5 (MEK5) 上游的两种异构体中，只有较长的 MEK5α 异构体能够有效激活 BMK1。我们生成了 MEK5α 的心脏特异性组成型活性形式（CA-MEK5α 转基因 (Tg) 小鼠），并观察到与野生型小鼠相比，Tg 心室中内源性 BMK1 激活和连接蛋白 43 过度磷酸化增加了 3 至 4 倍。 CA-MEK5α-Tg 小鼠表现出缺血/再灌注后左心室压力恢复明显加速。我们提出 BMK1 在保护心脏免受缺血/再灌注引起的心脏损伤方面的新作用。 (C) 2004 年由 Elsevier B.V. 代表欧洲生化学会联合会出版。
Big MAP kinase 1 (BMK1/ERK5) plays a critical role in pre-natal development of the cardiovascular system and post-natal eccentric hypertrophy of the heart. Of the two isoforms upstream of MAPK-kinase 5 (MEK5) known to exist, only the longer MEK5alpha isoform potently activates BMK1. We generated cardiac-specific constitutively active form of the MEK5alpha (CA-MEK5alpha transgenic (Tg) mice), and observed a 3 to 4-fold increase in endogenous BMK1 activation and hyperphosphorylation of connexin 43 in the ventricles of the Tg compared to wild-type mice. The CA-MEK5alpha-Tg-mice demonstrated a profoundly accelerated recovery of left ventricular developed pressure after ischemia/reperfusion. We propose a novel role for BMK1 in protecting the heart from ischemia/ reperfusion-induced cardiac injury. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.