title: Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes.
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.
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine Seoul 158-710, Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Yun
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Ara
authors.initials: A
authors.lastname: Jo
authors.forename: Jihee Lee
authors.initials: JL
authors.lastname: Kang
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D051243:Caveolin 2 / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D017628:Microglia / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051242:Caveolin 1; D051243:Caveolin 2; D017382:Reactive Oxygen Species; D048049:Extracellular Signal-Regulated MAP Kinases; D010744:Phosphoric Monoester Hydrolases; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D000072181:Inositol Polyphosphate 5-Phosphatases