Akt/Bad signaling and motor neuron survival after spinal cord injury

Fengshan Yu; Taku Sugawara; Carolina M. Maier; Lily B. Hsieh; Pak H. Chan

Neurobiology of Disease (Nov 2005)

Akt/Bad signaling and motor neuron survival after spinal cord injury

Fengshan Yu,
Taku Sugawara,
Carolina M. Maier,
Lily B. Hsieh,
Pak H. Chan

Affiliations

Fengshan Yu: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Taku Sugawara: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Carolina M. Maier: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Lily B. Hsieh: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305, USA
Pak H. Chan: Corresponding author. Neurosurgical Laboratories, Stanford University, 1201 Welch Road, MSLS #P314, Stanford, CA 94305-5487, USA. Fax: +1 650 498 4550.; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Neurosciences, Stanford University School of Medicine, Stanford, CA 94305, USA

Journal volume & issue: Vol. 20, no. 2
pp. 491 – 499

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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