Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes
Experimental & Molecular Medicine
; : 660-668, 2011.
Article
in En
| WPRIM
| ID: wpr-73120
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Phosphorylation
/
Gene Expression
/
Cell Line
/
Cells, Cultured
/
Astrocytes
/
Reactive Oxygen Species
/
Microglia
/
Phosphoric Monoester Hydrolases
/
Extracellular Signal-Regulated MAP Kinases
/
Caveolin 1
Limits:
Animals
/
Humans
Language:
En
Journal:
Experimental & Molecular Medicine
Year:
2011
Type:
Article