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
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 4.609
Times Cited 20
Mice SHPS-1 Knockout mice (RBRC01544)