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

Ji Hee Yun, Soo Jung Park, Ara Jo, Jihee Lee Kang, Ilo Jou, Jung Soo Park, Youn Hee Choi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish
Pages (from-to)660-668
Number of pages9
JournalExperimental and Molecular Medicine
Volume43
Issue number12
DOIs
StatePublished - 2011

Keywords

  • Astrocytes
  • Caveolin-1
  • Microglia
  • Protein tyrosine phosphatase non-receptor type 11
  • Reactive oxygen species

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