| RRC ID |
18094
|
| Author |
Wang L, Lu Y, Deng S, Zhang Y, Yang L, Guan Y, Matozaki T, Ohnishi H, Jiang H, Li H.
|
| Title |
SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress.
|
| Journal |
J Neurochem
|
| Abstract |
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.
|
| Volume |
122(4)
|
| Pages |
834-43
|
| Published |
2012-8-1
|
| DOI |
10.1111/j.1471-4159.2012.07818.x
|
| PMID |
22671569
|
| MeSH |
Animals
Blotting, Western
Brain / pathology
Brain Ischemia / genetics
Brain Ischemia / pathology
Carbon
Coloring Agents
Fluorescent Antibody Technique
Heme Oxygenase-1 / biosynthesis
In Situ Nick-End Labeling
Infarction, Middle Cerebral Artery / pathology
Ischemic Attack, Transient / genetics
Ischemic Attack, Transient / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2-Related Factor 2 / biosynthesis
NF-E2-Related Factor 2 / genetics
Nervous System Diseases / physiopathology
Oncogene Protein v-akt / metabolism
Oxidative Stress / genetics*
Oxidative Stress / physiology*
Real-Time Polymerase Chain Reaction
Receptors, Immunologic / genetics*
Receptors, Immunologic / physiology*
Stroke / genetics*
Stroke / pathology*
|
| IF |
4.066
|
| Times Cited |
27
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
NEUROSCIENCES
|
| Resource |
| Mice |
RBRC01544 |
