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

FEBS Lett. 2006 Apr 17;580(9):2311-6. doi: 10.1016/j.febslet.2006.03.043. Epub 2006 Mar 24.


The objective of this study was to identify proteins modified with O-linked N-acetylglucosamine (O-GlcNAc) in pancreatic beta-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 beta-cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • Caspase 3
  • Caspases / metabolism
  • Cell Death
  • Cell Line
  • Chaperonin 60 / metabolism*
  • Cytochromes c / metabolism
  • Cytoplasm / metabolism
  • Hyperglycemia / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Mitochondria / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Protein Transport
  • Rats
  • bcl-2-Associated X Protein / metabolism*


  • Bax protein, rat
  • Chaperonin 60
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Acetylglucosamine