Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades.
Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades.
复制标题
DOI：
10.21203/rs.3.rs-74078/v2
复制
发表时间：
2020-11
影响因子：
3.1
通讯作者：
Kazutoshi Hisano;S. Kawase;Tetsuhiko Mimura;Hironori Yoshida;H. Yamada;H. Haniu;T. Tsukahara;Taiga Kurihara;Y. Matsuda;N. Saito;Takeshi Uemura
中科院分区：
文献类型：
--
作者：
Kazutoshi Hisano;S. Kawase;Tetsuhiko Mimura;Hironori Yoshida;H. Yamada;H. Haniu;T. Tsukahara;Taiga Kurihara;Y. Matsuda;N. Saito;Takeshi Uemura
神经突生长在神经元回路形成和功能中是重要的，并且对于脑中创伤和疾病后神经元网络的再生是重要的。因此，识别和表征调节神经突生长的分子对于理解脑回路如何形成和功能以及神经系统疾病治疗的发展至关重要。在这项研究中，我们发现，结构不同的溶血磷脂酰乙醇胺（LPE）的种类，棕榈酰-LPE（16：0 LPE）和硬脂酰-LPE（18：0 LPE），刺激培养的皮层神经元的神经突起生长。有趣的是，YM-254890，一种Gq/11蛋白的抑制剂，抑制16：0 LPE刺激的神经突生长，但不抑制18：0 LPE刺激的神经突生长。相比之下，百日咳毒素，Gi/Go蛋白的抑制剂，抑制18：0 LPE刺激的神经突生长，但不16：0 LPE刺激的神经突生长。蛋白激酶C抑制剂对突起生长的影响也不同。此外，16：0 LPE和18：0 LPE均激活丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶1/2，但MAPK抑制剂的作用在16：0 LPE和18：0 LPE处理的培养物之间不同。总的来说，结果表明，结构上不同的LPE种类，16：0 LPE和18：0 LPE刺激神经突生长通过不同的信号级联在培养的皮层神经元和不同的G蛋白偶联受体参与这些过程。
Neurite outgrowth is important in neuronal circuit formation and functions, and for regeneration of neuronal networks following trauma and disease in the brain. Thus, identification and characterization of the molecules that regulate neurite outgrowth are essential for understanding how brain circuits form and function and for the development of treatment of neurological disorders. In this study, we found that structurally different lysophosphatidylethanolamine (LPE) species, palmitoyl-LPE (16:0 LPE) and stearoyl-LPE (18:0 LPE), stimulate neurite growth in cultured cortical neurons. Interestingly, YM-254890, an inhibitor of Gq/11 protein, inhibited 16:0 LPE-stimulated neurite outgrowth but not 18:0 LPE-stimulated neurite outgrowth. In contrast, pertussis toxin, an inhibitor of Gi/Go proteins, inhibited 18:0 LPE-stimulated neurite outgrowth but not 16:0 LPE-stimulated neurite outgrowth. The effects of protein kinase C inhibitors on neurite outgrowth were also different. In addition, both 16:0 LPE and 18:0 LPE activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2, but the effect of the MAPK inhibitor differed between the 16:0 LPE- and 18:0 LPE-treated cultures. Collectively, the results suggest that the structurally different LPE species, 16:0 LPE and 18:0 LPE stimulate neurite outgrowth through distinct signaling cascades in cultured cortical neurons and that distinct G protein-coupled receptors are involved in these processes.