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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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
Issue number9
Publication statusPublished - 2006 Apr 17


All Science Journal Classification (ASJC) codes

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

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