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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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14-3-3 Proteins / metabolism
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Animals
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Animals, Genetically Modified
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Cell Survival / genetics
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Disease Models, Animal
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Female
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Humans
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Motor Neurons / metabolism*
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Motor Neurons / pathology
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism
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Nerve Degeneration / physiopathology
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Oxidative Stress / physiology*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / genetics
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Spinal Cord / metabolism*
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Spinal Cord / pathology
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Spinal Cord / physiopathology
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Spinal Cord Injuries / genetics
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Spinal Cord Injuries / metabolism*
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Spinal Cord Injuries / physiopathology
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
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Superoxide Dismutase-1
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Up-Regulation / genetics
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bcl-Associated Death Protein / genetics
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bcl-Associated Death Protein / metabolism*
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bcl-X Protein / metabolism
Substances
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14-3-3 Proteins
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Bad protein, rat
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SOD1 protein, human
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bcl-Associated Death Protein
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bcl-X Protein
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Sod1 protein, rat
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Superoxide Dismutase
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Superoxide Dismutase-1
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt