Heat shock protein 60 modified with O-linked N-acetylglucosamine is involved in pancreatic β-cell death under hyperglycemic conditions

Hoe Suk Kim, Eun Mi Kim, Jiae Lee, Won Ho Yang, Tae Yoon Park, Young Min Kim, Jin Won Cho

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26 Citations (Scopus)

Abstract

The objective of this study was to identify proteins modified with O-linked N-acetylglucosamine (O-GlcNAc) in pancreatic β-cells and to understand their roles in cell death under hyperglycemic conditions. Here we report that heat shock protein 60 (HSP60) is modified with O-GlcNAc. Levels of O-GlcNAcylated HSP60 increased twofold in response to hyperglycemic conditions. HSP60 is a chaperonin known to bind to Bax in the cytoplasm under normoglycemic conditions. Under hyperglycemic conditions, Bax detached from O-GlcNAcylated HSP60 and translocated to mitochondria. Hyperglycemic conditions were also associated with cytochrome c release, caspase-3 activation, and cell death, suggesting that elevated O-GlcNAcylation of HSP60 interferes with HSP60-Bax interactions, leading to pancreatic β-cell death.

Original languageEnglish
Pages (from-to)2311-2316
Number of pages6
JournalFEBS Letters
Volume580
Issue number9
DOIs
Publication statusPublished - 2006 Apr 17

Bibliographical note

Funding Information:
This work was supported by grants from the Korea Science and Engineering Foundation (KOSEF) through the center for Protein Network Research Center (PNRC) at Yonsei University (R112000078020010), the Glycomics Research Program of MOST (2004-02130 to J.W.C.), the Korea Research Foundation Grant funded by the Korean Government (KRF-2004-005-C00112), and, in part, by the Yonsei University Research Fund of 1999. This work was made possible through the use of research facilities in Yonsei Center for Biotechnology.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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