AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats
AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats
复制标题
促红细胞生成素通过 AMP 激活的蛋白激酶依赖性诱导自噬可预防大鼠脊髓损伤
DOI：
10.1111/cns.12856
复制
发表时间：
2018
影响因子：
5.5
通讯作者：
Teng Hong-Lin
中科院分区：
文献类型：
--
作者：
Wang Peng;Xie Zhong-Dong;Xie Chang-Nan;Lin Chao-Wei;Wang Ji-Li;Xuan Li-Na;Zhang Chun-Wu;Wang Yu;Huang Zhi-Hui;Teng Hong-Lin
目的自噬被认为是脊髓损伤（SCI）治疗的一个很有前途的靶点。促红细胞生成素（EPO）已被证明在中枢神经系统（CNS）中表现出神经保护作用;然而，其保护SCI的分子机制仍不清楚。本研究旨在探讨EPO对SCI的神经保护作用是否通过AMP活化蛋白激酶（AMPK）信号通路介导的自噬来实现。结果EPO治疗可明显减少脊髓损伤后运动神经元的丢失，促进脊髓功能恢复。促红细胞生成素通过激活AMPK和失活mTOR信号转导显著增强SCI诱导的自噬。AMPK的抑制剂化合物C可以阻断EPO诱导的自噬和对SCI的有益作用，而AMPK的激活剂二甲双胍可以模拟EPO的作用。在体外研究中，EPO以AMPK依赖的方式增强缺氧诱导的自噬。结论AMPK依赖的自噬诱导有助于EPO对SCI的神经保护作用。
AimsAutophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP‐activated protein kinase (AMPK) signaling pathways.MethodsFunctional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry.ResultsTreatment with EPO significantly reduced the loss of motor neurons and improved the functional recovery following SCI. Erythropoietin significantly enhanced the SCI‐induced autophagy through activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound C, could block the EPO‐induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro studies, EPO enhanced the hypoxia‐induced autophagy in an AMPK‐dependent manner.ConclusionsThe AMPK‐dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.