PKC delta 激活可增加体外培养新生大鼠视网膜细胞的存活率：涉及神经营养因子和 M1 毒蕈碱受体。

PKC delta activation increases neonatal rat retinal cells survival in vitro: Involvement of neurotrophins and M1 muscarinic receptors.

机构信息

Programa de Neurociências, Universidade Federal Fluminense, RJ, Brazil.

Programa de Neurociências, Universidade Federal Fluminense, RJ, Brazil; Departamento de Neurobiologia, Instituto de Biologia, UFF, Outeiro de São João Batista s/n, Niterói, RJ, CEP: 24020-150, Brazil.

出版信息

Biochem Biophys Res Commun. 2018 Jun 12;500(4):917-923. doi: 10.1016/j.bbrc.2018.04.193. Epub 2018 May 1.

DOI:10.1016/j.bbrc.2018.04.193

PMID:29705702

Abstract

Protein kinase C (PKC) is a family of serine/threonine kinases related to several phenomena as cell proliferation, differentiation and survival. Our previous data demonstrated that treatment of axotomized neonatal rat retinal cell cultures for 48 h with phorbol 12-myristate 13-acetate (PMA), a PKC activator, increases retinal ganglion cells (RGCs) survival. Moreover, this treatment decreases M1 receptors (M1R) and modulates BDNF levels. The aim of this work was to assess the possible involvement of neurotrophins BDNF and NGF in the modulation of M1R levels induced by PKC activation, and its involvement on RGCs survival. Our results show that PMA (50 ng/mL) treatment, via PKC delta activation, modulates NGF, BDNF and M1R levels. BDNF and NGF mediate the decrease of M1R levels induced by PMA treatment. M1R activation is essential to PMA neuroprotective effect on RGCs as telenzepine (M1R selective antagonist) abolished it. Based on our results we suggest that PKC delta activation modulates neurotrophins levels by a signaling pathway that involves M1R activation and ultimately leading to an increase in RGCs survival in vitro.

摘要

蛋白激酶 C（PKC）是一类与细胞增殖、分化和存活等多种现象相关的丝氨酸/苏氨酸激酶。我们之前的数据表明，用 PKC 激活剂佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）处理体外培养的轴索切断的新生大鼠视网膜细胞 48 小时，可增加视网膜神经节细胞（RGC）的存活率。此外，这种处理还降低了 M1 受体（M1R）并调节了 BDNF 水平。本研究的目的是评估神经营养因子 BDNF 和 NGF 是否参与 PKC 激活诱导的 M1R 水平的调节，及其对 RGC 存活的影响。我们的结果表明，PKC delta 的激活通过 PMA 处理调节了 NGF、BDNF 和 M1R 的水平。BDNF 和 NGF 介导了 PMA 处理诱导的 M1R 水平降低。M1R 的激活对于 PMA 对 RGC 的神经保护作用是必需的，因为替仑辛（M1R 选择性拮抗剂）可消除其作用。基于我们的结果，我们认为 PKC delta 的激活通过涉及 M1R 激活的信号通路来调节神经营养因子的水平，最终导致体外 RGC 存活的增加。