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

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

doi:10.3858/emm.2011.43.12.075

Cited by 38 publications

(29 citation statements)

References 35 publications

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“…However, ROS regulation of SHP2 is controversial. Supporting a positive role for ROS on SHP2 activation, evidence shows that oxidative stress induces tyrosine phosphorylation of SHP2 at the C terminus through a mechanism involving the formation of lipid rafts and caveolin1 expression (39,40). Similar results have been demonstrated in response to exogenous hydrogen peroxide treatment (55) and the inhibition of lysyl oxidase (56).…”

Section: Discussionsupporting

confidence: 63%

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Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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Helicobacter pylori infection not only induces gastric inflammation but also increases the risk of gastric tumorigenesis. IFN-γ has antimicrobial effects; however, H. pylori infection elevates IFN-γ–mediated gastric inflammation and may suppress IFN-γ signaling as a strategy to avoid immune destruction through an as-yet-unknown mechanism. This study was aimed at investigating the mechanism of H. pylori–induced IFN-γ resistance. Postinfection of viable H. pylori decreased IFN-γ–activated signal transducers and activators of transcription 1 and IFN regulatory factor 1 not only in human gastric epithelial MKN45 and AZ-521 but also in human monocytic U937 cells. H. pylori caused an increase in the C-terminal tyrosine phosphorylation of Src homology-2 domain–containing phosphatase (SHP) 2. Pharmacologically and genetically inhibiting SHP2 reversed H. pylori–induced IFN-γ resistance. In contrast to a clinically isolated H. pylori strain HP238, the cytotoxin-associated gene A (CagA) isogenic mutant strain HP238CagAm failed to induce IFN-γ resistance, indicating that CagA regulates this effect. Notably, HP238 and HP238CagAm differently caused SHP2 phosphorylation; however, imaging and biochemical analyses demonstrated CagA-mediated membrane-associated binding with phosphorylated SHP2. CagA-independent generation of reactive oxygen species (ROS) contributed to H. pylori–induced SHP2 phosphorylation; however, ROS/SHP2 mediated IFN-γ resistance in a CagA-regulated manner. This finding not only provides an alternative mechanism for how CagA and ROS coregulate SHP2 activation but may also explain their roles in H. pylori–induced IFN-γ resistance.

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Section: Discussionsupporting

confidence: 63%

“…Recent findings indicate that ROS can induce tyrosine phosphorylation of SHP2 at the C terminus through the formation of lipid rafts (39,40). Notably, H. pylori infection also causes ROS generation (41).…”

Section: Ros Facilitates Tyrosine Phosphorylation Of Shp2 and Caga-dementioning

confidence: 99%

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Wang

Chen

Sheu

et al. 2014

The Journal of Immunology

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“…Cav-1 could protect neurons from hypoxic injury by promoting Src and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation (8). Additionally, Cav-1 was reported to be a positive regulator of hydrogen peroxide-induced ERK signaling in astrocytes (48). Therefore, the present study investigated the role of Cav-1 in the hypoxia-induced astrocyte injury.…”

mentioning

confidence: 93%

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway

Wang

Wen

et al. 2016

American Journal of Physiology-Cell Physiology

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Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downregulation of Cav-1 using Cav-1 small interfering RNA dramatically worsened astrocyte cell damage and impaired cellular glutamate uptake after OGD, whereas overexpression of Cav-1 with Cav-1 scaffolding domain peptide attenuated OGD-induced cell apoptosis. Mechanistically, the expressions of Ras-GTP, phospho-Raf, and phospho-ERK were sequestered in Cav-1 small interfering RNA-treated astrocytes, yet were stimulated after supplementation with caveolin peptide. MEK/ERK inhibitor U0126 remarkably blocked the Cav-1-induced counteraction against apoptosis following hypoxia, indicating Ras/Raf/ERK pathway is required for the Cav-1's prosurvival role. Together, these findings support Cav-1 as a checkpoint for the in hypoxia-induced astrocyte apoptosis and warrant further studies targeting Cav-1 to treat hypoxic-ischemic brain injury.

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“…We have reported that, in brain astrocytes, H 2 O 2 administration results in activation of signaling pathways by inducing protein phosphorylation via lipid rafts [33, 36, 37]. To ascertain whether lipid rafts are involved in H 2 O 2 -induced phosphorylation of STAT-6 in T cells, we pretreated Jurkat cells with methyl-β-cyclodextrin (MβCD), a cholesterol depleting agent that disrupts the integrity of lipid rafts.…”

Section: Resultsmentioning

confidence: 99%

Exogenous Hydrogen Peroxide Induces Lipid Raft-Mediated STAT-6 Activation in T Cells

Kim¹,

Lim²,

Jang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: CD4+ T cells are a critical component of the adaptive immune response. While the mechanisms controlling the differentiation of the Th1, Th17, and regulatory T cell subsets from naïve CD4+ T cells are well described, the factors that induce Th2 differentiation are still largely unknown. Methods: The effects of treatment with exogenous H₂O₂ on STAT-6 phosphorylation and activation in T cells were examined by immunoblotting, immunofluorescence and gel shift assay. Anti-CD3 antibody and methyl-β-cyclodextrin were utilized to induce lipid raft assembly and to investigate the involvement of lipid rafts, respectively. Results: Jurkat and EL-4 T cells that were exposed to H₂O₂ showed rapid and strong STAT-6 phosphorylation, and the extent of STAT-6 phosphorylation was enhanced by co-treatment with anti-CD3 antibody. The effect of H₂O₂ on STAT-6 phosphorylation and translocation was inhibited by disruption of lipid rafts. STAT-6 activation in response to H₂O₂ treatment regulated IL-4 gene expression, and this response was strengthened by treatment with anti-CD3. Conclusion: Our results indicate that reactive oxygen species such as H₂O₂ can act on upstream and initiating factors for activation of STAT-6 in T cells and contribute to formation of a positive feedback loop between STAT-6 and IL-4 in the Th2 differentiation process.

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

Cited by 38 publications

References 35 publications

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Helicobacter pylori Infection Activates Src Homology-2 Domain–Containing Phosphatase 2 To Suppress IFN-γ Signaling

Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway

Exogenous Hydrogen Peroxide Induces Lipid Raft-Mediated STAT-6 Activation in T Cells

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