SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress
Version of Record online: 9 JUL 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 122, Issue 4, pages 834–843, August 2012
How to Cite
Wang, L., Lu, Y., Deng, S., Zhang, Y., Yang, L., Guan, Y., Matozaki, T., Ohnishi, H., Jiang, H. and Li, H. (2012), SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress. Journal of Neurochemistry, 122: 834–843. doi: 10.1111/j.1471-4159.2012.07818.x
- Issue online: 17 JUL 2012
- Version of Record online: 9 JUL 2012
- Accepted manuscript online: 6 JUN 2012 12:21PM EST
- Received December 5, 2011; revised manuscript received May 31, 2012; accepted June 2, 2012.
- cerebral ischemia;
- heme oxygenase 1;
- nuclear factor-E2-related factor 2;
- oxidative stress;
J. Neurochem. (2012) 122, 834–843.
Src homology 2 domain–containing protein tyrosine phosphatase substrate–1 (SHPS-1), also known as Signal-regulatory protein alpha (SIRPα) or SIRPA is a transmembrane protein that is predominantly expressed in neurons, dendritic cells, and macrophages. This study was conducted to investigate the role of SHPS-1 in the oxidative stress and brain damage induced by acute focal cerebral ischemia. Wild-type (WT) and SHPS-1 mutant (MT) mice were subjected to middle cerebral artery occlusion (60 min) followed by reperfusion. SHPS-1 MT mice had significantly reduced infarct volumes and improved neurological function after brain ischemia. In addition, neural injury and oxidative stress were inhibited in SHPS-1 MT mice. The mRNA and protein levels of the antioxidant genes nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 were up-regulated in SHPS-1 MT mice. The SHPS-1 mutation suppressed the phosphorylation of SHP-1 and SHP-2 and increased the phosphorylation of Akt and GSK3β. These results provide the first demonstration that SHPS-1 plays an important role in the oxidative stress and brain injury induced by acute cerebral ischemia. The activation of Akt signaling and the up-regulation of Nrf2 and heme oxygenase 1 likely account for the protective effects that were observed in the SHPS-1 MT mice.