Yu Fengshan, Sugawara Taku, Maier Carolina M, Hsieh Lily B, Chan Pak H
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Neurobiol Dis. 2005 Nov;20(2):491-9. doi: 10.1016/j.nbd.2005.04.004.
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.
丝氨酸 - 苏氨酸激酶Akt是一种细胞存活信号通路，可使促凋亡的BCL - 2家族蛋白Bad失活，并促进脑缺血中的细胞存活。然而，脊髓损伤（SCI）后Akt / Bad信号通路的参与情况尚不确定。我们的结果表明，SCI后1天磷酸化Akt（丝氨酸 - 473）和磷酸化Bad（丝氨酸 - 136）显著上调。此外，磷酸化Akt和磷酸化Bad共定位于在SCI中存活的运动神经元中，并且抑制PI3 - K可降低磷酸化Akt和磷酸化Bad的表达。SCI后，Bad与胞质中14 - 3 - 3的二聚化增加，而线粒体中Bad / Bcl - XL的结合减少。我们进一步发现，与野生型大鼠相比，通过在大鼠中过表达SOD1降低氧化应激可增强SCI后磷酸化Akt、磷酸化Bad的表达、Bad / 14 - 3 - 3结合，并减少Bad / Bcl - XL结合。我们得出结论，氧化应激可能在调节SCI后Akt / Bad信号传导及随后的运动神经元存活中起作用。
