title: High-mobility group box 1 induces neuron autophagy in a rat spinal root avulsion model.
abstract: Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is implicated in various pathological states in the nervous system. High-mobility group box 1 (HMGB1) is an inflammatory mediator known to be released into the local microenvironment from damaged cells. However, whether autophagy is induced and exogenous HMGB1 is involved in the process of spinal root avulsion remain unclear. Here, we investigated the induction effect of autophagy and the possible role of HMGB1 during spinal root avulsion. It was found that autophagy was activated in the anterior horn of the spinal cord as represented by the increased expression of the autophagic marker microtubule-associated protein light chain 3-II (LC3-II), degradation of sequestosome 1 (p62), and formation of autophagosomes, and that autophagy was inhibited after intraperitoneal injection of anti-HMGB1-neutralizing antibodies in the rat spinal root avulsion model. In addition, HMGB1-induced autophagy and activated mitogen-activated protein kinases (MAPKs) in primary spinal neurons, including c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK), and p38MAPK. Inhibition of JNK or ERK activity significantly blocked the effect of HMGB1-induced autophagy in primary spinal neurons. Finally, HMGB1-induced autophagy increased cell viability in primary spinal neurons under oxygen-glucose deprivation conditions. The above results suggest that HMGB1 is a critical regulator of autophagy and HMGB1-induced autophagy plays an important role in protecting spinal neurons against injury, which may provide new insights into the pathophysiological process of spinal root avulsion.
authors.affiliation: Department of Orthopedic Trauma Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, China. Electronic address: hailangzhulei@126.com.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Electronic address: gaoxiangsoaring@163.com.
authors.forename: G
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Burn Surgery, Changhai Hospital, 168 Changhai Road, Yangpu District, Shanghai 200433, China. Electronic address: rei.sheng@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Department of Orthopedic Trauma Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, China. Electronic address: 254134536@qq.com.
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Orthopedic Trauma Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, China. Electronic address: aiminchen@aliyun.com.
authors.forename: A
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000906:Antibodies / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008159:Lumbar Vertebrae; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018696:Neuroprotective Agents
keywords: HMGB1; autophagy; spinal root avulsion