Role of STAT3 and Pl 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons
Role of STAT3 and Pl 3-Kinase/Akt in mediating the survival actions of cytokines on sensory neurons
复制标题
DOI：
10.1006/mcne.2001.1018
复制
发表时间：
2001-09-01
影响因子：
3.5
通讯作者：
Davies, AM
中科院分区：
文献类型：
--
作者：
Alonzi, T;Middleton, G;Davies, AM
细胞因子与gp130受体的结合激活STAT3、MEK/MAPK和PI3K/Akt信号通路。为了评估这些通路在促进细胞因子依赖性神经元存活中的相对重要性，我们在小鼠中有条件地灭活STAT3，并通过药理试剂和表达特定抑制蛋白来抑制培养神经元中的MEK、PI3K和Akt。STAT3的失活在体内增强了结节神经节细胞因子依赖性感觉神经元的死亡，并在体外显著降低了这些神经元对CNTF和LIF的反应。PI3K抑制剂LY294002显著降低了这些神经元对CNTF的反应，而MEK抑制剂PD98059则没有，此外，PI3K -显性阴性、Akt -显性阴性和Ruk（一种天然PI3K抑制剂）的过表达也起到了同样的作用(1)。这些结果表明，STAT3和PI3K/Akt信号在介导神经元对细胞因子的生存反应中起主要作用。
The binding of cytokines to the gp130 receptor activates the STAT3, MEK/MAPK, and PI3K/Akt signalling pathways. To assess the relative importance of these pathways in promoting the survival of cytokine-dependent neurons, we conditionally inactivated STAT3 in mice an inhibited MEK, PI3K, and Akt in cultured neurons using pharmacological reagents and by expressing specific inhibitory proteins. Inactivation of STAT3 enhanced the death of the cytokine-dependent sensory neurons of the nodose ganglion in vivo and substantially reduced the response of these neurons to CNTF and LIF in vitro. LY294002, an inhibitor of PI3K, but not PD98059, an inhibitor of MEK, markedly reduced the response of these neurons to CNTF, as did dominant-negative PI3K, dominant-negative Akt, and overexpression of Ruk(1) (a natural PI3K inhibitor). These results demonstrate that STAT3 and PI3K/Akt signalling play major roles in mediating the survival response of neurons to cytokines.