Erythropoietin inhibits osmotic swelling of retinal glial cells by Janus kinase- and extracellular signal-regulated kinases1/2-mediated release of vascular endothelial growth factor
Erythropoietin inhibits osmotic swelling of retinal glial cells by Janus kinase- and extracellular signal-regulated kinases1/2-mediated release of vascular endothelial growth factor
复制标题
促红细胞生成素通过 Janus 激酶和细胞外信号调节激酶 1/2 介导的血管内皮生长因子释放抑制视网膜神经胶质细胞的渗透性肿胀
DOI：
10.1016/j.neuroscience.2009.11.035
复制
发表时间：
2010
期刊：
影响因子：
3.3
通讯作者：
Bringmann A
中科院分区：
文献类型：
--
作者：
Krügel K;Wurm A;Linnertz R;Pannicke T;Wiedemann P;Reichenbach A;Bringmann A
视网膜神经胶质细胞的体积稳态是由离子通道开放的自分泌嘌呤能机制介导的，其响应于细胞外渗透压的降低而被激活。在这里，我们表明，促红细胞生成素（EPO）防止渗透性肿胀的神经胶质细胞体在视网膜切片和分离的神经胶质细胞从控制和糖尿病大鼠，与一个半最大的效果在0.01 nM。EPO引起的下游信号传导包括从细胞释放血管内皮生长因子，其被Janus激酶和细胞外信号调节激酶（ERK）1/2抑制剂阻断。含激酶插入结构域的受体/fms样酪氨酸激酶1（KDR/flk-1）的反式激活引起谷氨酸的钙依赖性胞吐释放，随后激活I/II组代谢型谷氨酸受体，这导致ATP和腺苷从细胞中的钙非依赖性释放。该级联反应的最后一步是腺苷A1受体的激活，导致蛋白激酶A和磷酸肌醇3激酶介导的钾和氯通道开放。促红细胞生成素受体蛋白的免疫组织化学定位于视网膜内层和光感受器内节。在分离的神经胶质细胞中，EPO受体蛋白选择性地定位于原位穿过内核层的纤维。抑制胶质细胞肿胀可能有助于EPO在病理条件下对视网膜的神经保护作用。
The volume homeostasis of retinal glial cells is mediated by an autocrine purinergic mechanism of ion channel opening which is activated in response to a decrease in the extracellular osmolarity. Here, we show that erythropoietin (EPO) prevents the osmotic swelling of glial somata in retinal slices and of isolated glial cells from control and diabetic rats, with a half-maximal effect at ∼0.01 nM. The downstream signaling evoked by EPO includes a release of vascular endothelial growth factor from the cells which was blocked by Janus kinase and extracellular signal-regulated kinases (ERK)1/2 inhibitors. Transactivation of kinase insert domain-containing receptor/fms-like tyrosine kinase 1 (KDR/flk-1) evokes a calcium-dependent, exocytotic release of glutamate, followed by activation of group I/II metabotropic glutamate receptors which results in calcium-independent release of ATP and adenosine from the cells. The final step in this cascade is the activation of adenosine A1receptors which results in protein kinase A- and phosphoinositide 3-kinase-mediated opening of potassium and chloride channels. EPO receptor protein was immunohistochemically localized to the inner retina and photoreceptor inner segments. In isolated glial cells, EPO receptor protein is selectively localized to fibers which traverse the inner nuclear layer in situ. Inhibition of glial swelling might contribute to the neuroprotective action of EPO in the retina under pathological conditions.
登录
查看更多内容
胶质细胞衍生的谷氨酸介导视网膜自分泌细胞体积调节：VEGF 的激活
影响因子：
4.7
作者：
A. Wurm;T. Pannicke;P. Wiedemann;A. Reichenbach;A. Bringmann
通讯作者：
A. Bringmann
影响因子：
2.5
作者：
DUDEK, FE;OBENAUS, A;TASKER, JG
通讯作者：
TASKER, JG
视网膜整体中 Müller 胶质细胞的活体染料选择性染色
影响因子：
6.2
作者：
Ortrud Uckermann;I. Iandiev;M. Francke;K. Franze;J. Grosche;S. Wolf;L. Kohen;P. Wiedemann;A. Reichenbach;A. Bringmann
通讯作者：
A. Bringmann
DOI：
10.1523/jneurosci.18-11-04022.1998
发表时间：
1998-06
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
E. Newman;K. Zahs
通讯作者：
E. Newman;K. Zahs
影响因子：
3.7
作者：
D. Wojchowski;R. Gregory;Chris P. Miller;Ajay K. Pandit;T. Pircher
通讯作者：
D. Wojchowski;R. Gregory;Chris P. Miller;Ajay K. Pandit;T. Pircher