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Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes
- Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes
- Park S.J.; Kim H.Y.; Kim H.; Park S.M.; Joe E.-h.; Jou I.; Choi Y.-H.
- Ewha Authors
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- Journal Title
- Free Radical Biology and Medicine
- Free Radical Biology and Medicine vol. 46, no. 12, pp. 1694 - 1702
- SCI; SCIE; SCOPUS
- Document Type
- Several protein phosphatases are involved in neuroprotection in response to ischemic brain injury. Here, we report that reactive oxygen species (ROS)-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 through lipid rafts in rat primary astrocytes. SHP-2 was transiently phosphorylated during hypoxia/reoxygenation, an effect abrogated by a ROS scavenger and an NADPH oxidase inhibitor. Additionally, exogenous treatment with hydrogen peroxide (H2O2) triggered SHP-2 phosphorylation in a time- and dose-dependent manner and led to its translocation into lipid rafts. H2O2-mediated SHP-2 phosphorylation and translocation were inhibited by filipin III and methyl-β-cyclodextrin (MCD), lipid-raft-disrupting agents. In the presence of H2O2, SHP-2 formed a complex with STAT-3 and reduced the steady-state STAT-3 phosphorylation level. Interestingly, the effect of H2O2 on SHP-2 phosphorylation was cell-type specific. Remarkably, SHP-2 phosphorylation was induced strongly by H2O2 in astrocytes, but barely detectable in microglia. Our results collectively indicate that SHP-2 is activated by ROS-mediated oxidative stress in astrocytes and functions as a component of the raft-mediated signaling pathway that acts through dephosphorylation and inactivation of other phosphotyrosine proteins, such as STAT-3. © 2009 Elsevier Inc. All rights reserved.
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