Peng Wang1,2, Zhong-Dong Xie3, Chang-Nan Xie1,4, Chao-Wei Lin1, Ji-Li Wang5, Li-Na Xuan4, Chun-Wu Zhang1, Yu Wang1, Zhi-Hui Huang4, Hong-Lin Teng1. 1. Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China. 2. Department of Emergency Medicine, Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhejiang, China. 3. Department of Gastrointestinal Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China. 4. Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China. 5. Department of Pathology, Zhejiang University First Affiliated Hospital, Hangzhou, Zhejiang, China.
Abstract
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.
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.
Authors: M L Brines; P Ghezzi; S Keenan; D Agnello; N C de Lanerolle; C Cerami; L M Itri; A Cerami Journal: Proc Natl Acad Sci U S A Date: 2000-09-12 Impact factor: 11.205
Authors: Paul B Yu; Charles C Hong; Chetana Sachidanandan; Jodie L Babitt; Donna Y Deng; Stefan A Hoyng; Herbert Y Lin; Kenneth D Bloch; Randall T Peterson Journal: Nat Chem Biol Date: 2007-11-18 Impact factor: 15.040
Authors: Guowu Hu; Travis McQuiston; Amélie Bernard; Yoon-Dong Park; Jin Qiu; Ali Vural; Nannan Zhang; Scott R Waterman; Nathan H Blewett; Timothy G Myers; Richard J Maraia; John H Kehrl; Gulbu Uzel; Daniel J Klionsky; Peter R Williamson Journal: Autophagy Date: 2015 Impact factor: 16.016