Inhibition of glycogen synthase kinase 3β suppresses coxsackievirus-induced cytopathic effect and apoptosis via stabilization of β-catenin

J. Yuan, J. Zhang, B. W. Wong, X. Si, J. Wong, D. Yang, H. Luo

Research output: Contribution to journalArticle

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Abstract

Coxsackievirus B3 (CVB3), a common human pathogen for viral myocarditis, induces a direct cytopathic effect (CPE) and apoptosis on infected cells. To elucidate the mechanisms that contribute to these processes, we studied the role of glycogen synthase kinase 3β (GSK3β). GSK3β activity was significantly increased after CVB3 infection and addition of tyrosine kinase inhibitors blocked CVB3-triggered GSK3β activation. Inhibition of caspase activity had no inhibitory effect on CVB3-induced CPE; however, blockage of GSK3β activation attenuated both CVB3-induced CPE and apoptosis. We further showed that CVB3 infection resulted in reduced β-catenin protein expression, and GSK3β inhibition led to the accumulation and nuclear translocation of β-catenin. Finally, we found that CVB3-induced CPE and apoptosis were significantly reduced in cells stably overexpressing β-catenin. Taken together, our results demonstrate that CVB3 infection stimulates GSK3β activity via a tyrosine kinase-dependent mechanism, which contributes to CVB3-induced CPE and apoptosis through dysregulation of β-catenin.

Original languageEnglish (US)
Pages (from-to)1097-1106
Number of pages10
JournalCell Death and Differentiation
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2005

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Glycogen Synthase Kinase 3
Catenins
Enterovirus
Coxsackievirus Infections
Apoptosis
Protein-Tyrosine Kinases
Myocarditis
Caspases

Keywords

  • Apoptosis
  • Coxsackievirus
  • Cytopathic effect
  • GSK3β
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Inhibition of glycogen synthase kinase 3β suppresses coxsackievirus-induced cytopathic effect and apoptosis via stabilization of β-catenin. / Yuan, J.; Zhang, J.; Wong, B. W.; Si, X.; Wong, J.; Yang, D.; Luo, H.

In: Cell Death and Differentiation, Vol. 12, No. 8, 01.08.2005, p. 1097-1106.

Research output: Contribution to journalArticle

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AU - Yang, D.

AU - Luo, H.

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