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 journalArticlepeer-review

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

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation funded by the Korean Government (R0A-2007-000-20011-0), WCU (World Class University) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R31-2008-000-10086-0), and partly by KRF-2006-005-J04502. Additionally, S.Y.P., S.J. and J.G.K. are fellowship awardees of the Brain Korea 21 program. This work was made possible through the use of research facilities in the Yonsei Center for Biotechnology.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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