Cytokines promote motoneuron survival through the janus kinase-dependent activation of the phosphatidylinositol 3-kinase pathway
Cytokines promote motoneuron survival through the janus kinase-dependent activation of the phosphatidylinositol 3-kinase pathway
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DOI：
10.1006/mcne.2001.1058
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发表时间：
2001-12-01
影响因子：
3.5
通讯作者：
Comella, JX
中科院分区：
文献类型：
--
作者：
Dolcet, X;Soler, RM;Comella, JX
为了确定纤毛神经营养因子和心营养因子-1细胞因子对运动神经元的存活影响是由哪些细胞内通路介导的，我们研究了Jak/STAT、PI 3-激酶/Akt和ERK通路的激活。在较短的时间点，细胞因子诱导STAT3和ERK的激活，但不诱导PI 3-激酶的激活。Jak3抑制剂抑制细胞因子和肌肉提取物诱导的存活。相比之下，MEK抑制剂PD 98059不能阻止细胞因子诱导的存活，这表明ERK与此无关。令人惊讶的是，PI 3-激酶抑制剂LY 294002阻止了细胞因子的促生存作用。当在细胞因子处理后的后期进行PI 3-激酶活性测定时，与对照培养相比，观察到显着增加。这种延迟的活性增加可以通过蛋白质合成或Jak3抑制剂完全阻止。总的来说，这些结果表明细胞因子通过PI 3-激酶激活诱导运动神经元存活，这需要依赖于Jak途径的从头蛋白合成。
To determine which intracellular pathways mediate the survival effects of ciliary neurotrophic factor and cardiotrophin-1 cytokines on motoneurons, we studied the activation of the Jak/STAT, the PI 3-kinase/Akt, and the ERK pathways. At shorter time points, cytokines induced the activation of STAT3 and ERK, but not PI 3-kinase. Jak3 inhibitor suppressed cytokine- and muscle extract-induced survival. In contrast, PD 98059, a MEK inhibitor, was not able to prevent cytokine-induced survival, demonstrating that ERK is not involved. Surprisingly, the PI 3-kinase inhibitor LY 294002 prevented the survival-promoting effects of cytokines. When assays of PI 3-kinase activity were performed at later stages following cytokine treatment a significant increase was observed compared to control cultures. This delayed increase of activity could be completely prevented by treatment with protein synthesis or Jak3 inhibitors. Collectively, these results demonstrate that cytokines induce motoneuron survival through a PI 3-kinase activation requiring de novo protein synthesis dependent on Jak pathway.