title: Akt/Bad signaling and motor neuron survival after spinal cord injury.
abstract: The serine-threonine kinase Akt is a cell survival signaling pathway that inactivates the proapoptotic BCL-2 family protein Bad and promotes cell survival in cerebral ischemia. Involvement of the Akt/Bad signaling pathway after spinal cord injury (SCI) is, however, uncertain. Our results showed that phospho-Akt (serine-473) and phospho-Bad (serine-136) were significantly upregulated at 1 day after SCI. In addition, phospho-Akt and phospho-Bad were colocalized in motor neurons that survived SCI and inhibition of PI3-K reduced expression of phospho-Akt and phospho-Bad. Dimerization of Bad with 14-3-3 in the cytosol was increased whereas Bad/Bcl-XL binding in the mitochondria was decreased after SCI. We further found that reduced oxidative stress by SOD1 overexpression in rats enhanced the expression of phospho-Akt, phospho-Bad, Bad/14-3-3 binding and reduced Bad/Bcl-XL binding after SCI, as compared to wild-type rats. We conclude that oxidative stress may play a role in modulating Akt/Bad signaling and subsequent motor neuron survival after SCI.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Fengshan
authors.initials: F
authors.lastname: Yu
authors.forename: Taku
authors.initials: T
authors.lastname: Sugawara
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Maier
authors.forename: Lily B
authors.initials: LB
authors.lastname: Hsieh
authors.forename: Pak H
authors.initials: PH
authors.lastname: Chan
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; C494821:Bad protein, rat; C000606290:SOD1 protein, human; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt