AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats.

Autor: Wang P; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.; Department of Emergency Medicine, Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhejiang, China., Xie ZD; Department of Gastrointestinal Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China., Xie CN; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.; Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China., Lin CW; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China., Wang JL; Department of Pathology, Zhejiang University First Affiliated Hospital, Hangzhou, Zhejiang, China., Xuan LN; Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China., Zhang CW; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China., Wang Y; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China., Huang ZH; Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China., Teng HL; Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2018 Dec; Vol. 24 (12), pp. 1185-1195. Date of Electronic Publication: 2018 Apr 15.
DOI: 10.1111/cns.12856
Abstrakt: Aims: Autophagy 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.
Methods: Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry.
Results: Treatment 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.
Conclusions: The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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