Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes.
10.3858/emm.2011.43.12.075
- Author:
Ji Hee YUN
1
;
Soo Jung PARK
;
Ara JO
;
Jihee Lee KANG
;
Ilo JOU
;
Jung Soo PARK
;
Youn Hee CHOI
Author Information
1. Department of Physiology, Ewha Womans University School of Medicine, Seoul 158-710, Korea. yc@ewha.ac.kr, jihee@ewha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
astrocytes;
caveolin-1;
microglia;
protein tyrosine phosphatase, non-receptor type 11;
reactive oxygen species
- MeSH:
Animals;
Astrocytes/*metabolism;
Caveolin 1/*genetics/metabolism;
Caveolin 2/genetics;
Cell Line;
Cells, Cultured;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Gene Expression;
Humans;
Microglia/metabolism;
Phosphoric Monoester Hydrolases/*metabolism;
Phosphorylation;
Protein Tyrosine Phosphatase, Non-Receptor Type 11/*metabolism;
Rats;
Reactive Oxygen Species/*metabolism
- From:Experimental & Molecular Medicine
2011;43(12):660-668
- CountryRepublic of Korea
- Language:English
-
Abstract:
Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress.
