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Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes.

Park, SJ | Kim, HY  | Kim, H | Park, SM  | Joe, EH  | Jou, I  | Choi, YH
Free radical biology & medicine, 46(12). : 1694-1702, 2009
Journal Title
Free radical biology & medicine
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 (H(2)O(2)) triggered SHP-2 phosphorylation in a time- and dose-dependent manner and led to its translocation into lipid rafts. H(2)O(2)-mediated SHP-2 phosphorylation and translocation were inhibited by filipin III and methyl-beta-cyclodextrin (MCD), lipid-raft-disrupting agents. In the presence of H(2)O(2), SHP-2 formed a complex with STAT-3 and reduced the steady-state STAT-3 phosphorylation level. Interestingly, the effect of H(2)O(2) on SHP-2 phosphorylation was cell-type specific. Remarkably, SHP-2 phosphorylation was induced strongly by H(2)O(2) 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.

Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
김, 희영  |  박, 상면  |  조, 은혜  |  주, 일로
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