Heat shock protein 60 modified with O-linked N-acetylglucosamine is involved in pancreatic beta-cell death under hyperglycemic conditions.
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.
Kim
Hoe Suk
HS
Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Kim
Eun Mi
EM
Lee
Jiae
J
Yang
Won Ho
WH
Park
Tae Yoon
TY
Kim
Young Min
YM
Cho
Jin Won
JW
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
C494828:Bax protein, rat; D018834:Chaperonin 60; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D000117:Acetylglucosamine