O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation

Won Ho Yang, Sang Yoon Park, Suena Ji, Jeong Gu Kang, Ji Eun Kim, Hyundong Song, Inhee Mook-Jung, Kwang-Min Choe, Jin Won Cho

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hyperglycemia induces activation of glutathione peroxidase 1 (GPX1), an anti-oxidant enzyme essential for cell survival during oxidative stress. However, the mechanism of GPX1 activation is unclear. Here, we report that hyperglycemia-induced protein glycosylation by O-linked N-acetylglucosamine (O-GlcNAc) is crucial for activation of GPX1 and for its binding to c-Abl and Arg kinases. GPX1 itself is modified with O-GlcNAc on its C-terminus. We also demonstrate that pharmacological injection of the O-GlcNAcase inhibitor NTZ induces GPX1 activation in the mouse liver. Our findings suggest a crucial role for GPX1 and its O-GlcNAc modification in hyperglycemia and diabetes mellitus.

Original languageEnglish
Pages (from-to)756-761
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume391
Issue number1
DOIs
Publication statusPublished - 2010 Jan 1

Fingerprint

Hyperglycemia
Chemical activation
nitazoxanide
Glycosylation
Oxidative stress
Acetylglucosamine
Medical problems
Oxidants
Liver
glutathione peroxidase GPX1
Cell Survival
Diabetes Mellitus
Oxidative Stress
Phosphotransferases
Cells
Pharmacology
Injections
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yang, Won Ho ; Park, Sang Yoon ; Ji, Suena ; Kang, Jeong Gu ; Kim, Ji Eun ; Song, Hyundong ; Mook-Jung, Inhee ; Choe, Kwang-Min ; Cho, Jin Won. / O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation. In: Biochemical and Biophysical Research Communications. 2010 ; Vol. 391, No. 1. pp. 756-761.
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O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation. / Yang, Won Ho; Park, Sang Yoon; Ji, Suena; Kang, Jeong Gu; Kim, Ji Eun; Song, Hyundong; Mook-Jung, Inhee; Choe, Kwang-Min; Cho, Jin Won.

In: Biochemical and Biophysical Research Communications, Vol. 391, No. 1, 01.01.2010, p. 756-761.

Research output: Contribution to journalArticle

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AU - Yang, Won Ho

AU - Park, Sang Yoon

AU - Ji, Suena

AU - Kang, Jeong Gu

AU - Kim, Ji Eun

AU - Song, Hyundong

AU - Mook-Jung, Inhee

AU - Choe, Kwang-Min

AU - Cho, Jin Won

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AB - Hyperglycemia induces activation of glutathione peroxidase 1 (GPX1), an anti-oxidant enzyme essential for cell survival during oxidative stress. However, the mechanism of GPX1 activation is unclear. Here, we report that hyperglycemia-induced protein glycosylation by O-linked N-acetylglucosamine (O-GlcNAc) is crucial for activation of GPX1 and for its binding to c-Abl and Arg kinases. GPX1 itself is modified with O-GlcNAc on its C-terminus. We also demonstrate that pharmacological injection of the O-GlcNAcase inhibitor NTZ induces GPX1 activation in the mouse liver. Our findings suggest a crucial role for GPX1 and its O-GlcNAc modification in hyperglycemia and diabetes mellitus.

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