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SHPS‐1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress
Author(s) -
Wang Lang,
Lu Yanyun,
Deng Shan,
Zhang Yan,
Yang Li,
Guan Yu,
Matozaki Takashi,
Ohnishi Hiroshi,
Jiang Hong,
Li Hongliang
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07818.x
Subject(s) - oxidative stress , neuroprotection , protein kinase b , medicine , endocrinology , tyrosine phosphorylation , protein tyrosine phosphatase , heme oxygenase , phosphorylation , microbiology and biotechnology , biology , chemistry , heme , biochemistry , enzyme
J. Neurochem. (2012) 122 , 834–843. 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.