| First Author | Wang L | Year | 2012 |
| Journal | J Neurochem | Volume | 122 |
| Issue | 4 | Pages | 834-43 |
| PubMed ID | 22671569 | Mgi Jnum | J:187521 |
| Mgi Id | MGI:5437383 | Doi | 10.1111/j.1471-4159.2012.07818.x |
| Citation | Wang L, et al. (2012) SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress. J Neurochem 122(4):834-43 |
| abstractText | Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), also known as Signal-regulatory protein alpha (SIRPalpha) 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 GSK3beta. 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. |
