Tissue hypoxia activates JNK in the liver during hemorrhagic shock
Tissue hypoxia activates JNK in the liver during hemorrhagic shock
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DOI：
10.1097/01.shk.0000140660.78744.bf
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发表时间：
2004-10-01
期刊：
影响因子：
3.1
通讯作者：
Billiar, TR
中科院分区：
文献类型：
--
作者：
McCloskey, CA;Kameneva, MV;Billiar, TR
最早的信号通路，负责启动全身反应，出血性休克（HS）仍然很差的特点。我们研究了有丝分裂原活化蛋白（MAP）激酶C-JUN N-末端激酶（JNK）的参与及其在肝脏中的激活，作为出血开始后不久对组织缺氧的早期反应。在本研究中，小鼠出血至25 mmHg持续30分钟导致肝脏内JNK磷酸化显著增加（2.1倍）。在40 mmHg下加压1 h的大鼠中，结果相似。单独缺氧，复制热隔离肝缺血在体内或肝细胞培养下1%的氧气，也导致JNK磷酸化。最后，通过在大鼠HS模型中用血溶性减阻聚合物（DRP）预处理来保存组织灌注和氧合，防止肝脏中JNK的磷酸化。这些结果确定了组织缺氧作为激活出血后肝脏中早期信号传导事件的关键因素，如通过JNK磷酸化测量的。
The earliest signaling pathways responsible for initiating the systemic response to hemorrhagic shock (HS) remain poorly characterized. We have investigated the involvement of the mitogen-activated protein (MAP) kinase C-JUN N-terminal kinase (JNK) and its activation in the liver as an early response to tissue hypoxia soon after the initiation of hemorrhage. In the present studies, hemorrhage of mice to 25 mmHg for 30 min resulted in a significant (2.1-fold) increase in JNK phosphorylation within the liver. Results were similar in rats hemorrhaged to 40 mmHg for 1 h. Hypoxia alone, replicated by warm isolated hepatic ischemia in vivo or hepatocytes cultured under 1% oxygen, also resulted in JNK phosphorylation. Finally, preservation of tissue perfusion and oxygenation by pretreatment with a blood-soluble drag-reducing polymer (DRP) in the rat HS model prevented phosphorylation of JNK in the liver. These results identify tissue hypoxia as a key factor in activating early signaling events in the liver following hemorrhage, as measured by JNK phosphorylation.