Akt/Bad signaling and motor neuron survival after spinal cord injury.
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.
Yu
Fengshan
F
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sugawara
Taku
T
Maier
Carolina M
CM
Hsieh
Lily B
LB
Chan
Pak H
PH
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
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