Exp Mol Med.  2011 Dec;43(12):660-668. 10.3858/emm.2011.43.12.075.

Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes

• Yun JH
• Park SJ
• Jo A
• Kang JL
• Jou I
• Park JS
• Choi YH

• KMID: 1058703
• DOI: http://doi.org/10.3858/emm.2011.43.12.075

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.

Keyword

astrocytes; caveolin-1; microglia; protein tyrosine phosphatase, non-receptor type 11; reactive oxygen species

MeSH Terms

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