title: Prohibitin 1 gene delivery promotes functional recovery in rats with spinal cord injury.
abstract: Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. Then, we hypothesized that PHB1 overexpression by delivery of Ad-PHB1 could result in neuroprotection and promote functional recovery following SCI. Briefly, Wistar rats received a 35-g clip-compression injury and were administered Ad-PHB1 or Ad immediately following SCI. It was found that Ad-PHB1 administration significantly improved locomotor function and increased pain tolerance in rats with SCI. Furthermore, Ad-PHB1 administration following SCI attenuated axonal degradation and increased neuron sparing. Ad-PHB1 administration following SCI reduced apoptosis through inhibiting the Bcl-2/Bax/caspase-3 pathway. Ad-PHB1 administration following SCI suppressed endoplasmic reticulum stress, evidenced by reduced mRNA levels of CCAAT enhancer binding protein homologous protein, chaperone-ucose-regulated protein 78, and X-box protein 1. Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
authors.forename: J-D
authors.initials: JD
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
authors.forename: H-D
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China. Electronic address: houshx2014@hotmail.com.
authors.forename: S-X
authors.initials: SX
authors.lastname: Hou
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018450:Disease Progression; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D005822:Genetic Vectors; D006930:Hyperalgesia / Q000188:drug therapy; D008124:Locomotion / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000627:therapeutic use*; D000091402:Prohibitins; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D000091402:Prohibitins; D012097:Repressor Proteins
keywords: apoptosis; endoplasmic reticulum stress; mitochondria; prohibitin 1; spinal cord injury