title: Heme oxygenase-1 promotes neuron survival through down-regulation of neuronal NLRP1 expression after spinal cord injury.
abstract: BACKGROUND
  Understanding the mechanisms underlying neuronal death in spinal cord injury (SCI) and developing novel therapeutic approaches for SCI-induced damage are critical for functional recovery. Here we investigated the role of heme oxygenase-1 (HO-1) in neuroprotection after SCI.
  
  
  METHODS
  Adeno-associated virus expressing HO-1 was prepared and injected into rat spinal cords before SCI model was performed. HO-1 expression, inflammasome activation, and the presence of inflammatory cytokines were determined by quantitative polymerase chain reaction, immunohistological staining, immunoblot, and immunoprecipitation. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling. The hindlimb locomotor function was evaluated for extent of neurologic damage. In an in vitro model, hydrogen peroxide was used to induce similar inflammasome activation in cultured primary spinal cord neurons, followed by evaluation of above parameters with or without transduction of HO-1-expressing adeno-associated virus.
  
  
  RESULTS
  Endogenous HO-1 expression was found in spinal cord neurons after SCI in vivo, in association with the expression of Nod-like receptor protein 1 (NLRP1) and the formation of NLRP1 inflammasomes. Administration of HO-1-expressing adeno-associated virus effectively decreased expression of NLRP1, therefore alleviating NLRP1 inflammasome-induced neuronal death and improving functional recovery. In the in vitro model, exogenous HO-1 expression protected neurons from hydrogen peroxide-induced neuronal death by inhibiting NLRP1 expression. In addition, HO-1 inhibited expression of activating transcription factor 4 (ATF4), which is a transcription factor regulating NLRP1 expression.
  
  
  CONCLUSIONS
  HO-1 protects spinal cord neurons after SCI through inhibiting NLRP1 inflammasome formation.
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, China. okoklwp@126.com.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Lin
authors.affiliation: Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361009, China. 8137605@qq.com.
authors.forename: Gong-Peng
authors.initials: GP
authors.lastname: Xiong
authors.affiliation: Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China. opopop_009@163.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Orthopedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, China. 390036557@qq.com.
authors.forename: Xuan-Wei
authors.initials: XW
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, China. 605564497@qq.com.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, China. 14137921@qq.com.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Orthopedic Surgery, the Second Affiliated Hospital, Fujian Medical University, Quanzhou, 362000, China. qingfengke55@126.com.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Ke
authors.affiliation: Department of Orthopedic Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, China. jianhua0918@126.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lin
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D015536:Down-Regulation; D005822:Genetic Vectors; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D058847:Inflammasomes; D008124:Locomotion; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: C497110:Atf4 protein, rat; D058847:Inflammasomes; D009419:Nerve Tissue Proteins; C526260:Nlrp1a protein, rat; D051701:Activating Transcription Factor 4; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1