1. SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress.
- Author
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Wang L, Lu Y, Deng S, Zhang Y, Yang L, Guan Y, Matozaki T, Ohnishi H, Jiang H, and Li H
- Subjects
- 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, Real-Time Polymerase Chain Reaction, Oxidative Stress genetics, Oxidative Stress physiology, Receptors, Immunologic genetics, Receptors, Immunologic physiology, Stroke genetics, Stroke pathology
- 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., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)
- Published
- 2012
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