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Proteomic analysis of O-GlcNAc modifications derived from streptozotocin and glucosamine induced beta-cell apoptosis.

Authors
Park, J; Kwon, H; Kang, Y; Kim, Y
Citation
Journal of biochemistry and molecular biology, 40(6):1058-1068, 2007
Journal Title
Journal of biochemistry and molecular biology
ISSN
1225-86870219-1024
Abstract
The post-translational modifications of Ser and Thr residues by O-linked beta-N-acetylglucosamine (O-GlcNAc), i.e., O-GlcNAcylation, is considered a key means of regulating signaling, in a manner analogous to protein phosphorylation. Furthermore, it has been suggested that the increased flux of glucose through the hexosamine biosynthetic pathway (HBP) stimulates O-GlcNAcylation, and that this may be responsible for many of the manifestations of type 2 diabetes mellitus. To determine whether excessive O-GlcNAcylation of target proteins results in pancreatic beta cell dysfunction, we increased nucleocytoplasmic protein O-GlcNAcylation levels in beta cells by exposing them to streptozotocin and/or glucosamine. Streptozotocin and glucosamine co-treatment increased OGlcNAcylated proteomic patterns as assessed by immunoblotting, and these increases in nuclear and cytoplasmic protein O-GlcNAcylations were accompanied by impaired insulin secretion and enhanced apoptosis in pancreatic beta cells. This observed beta cell dysfunction prompted us to examine Akt and Bcl-2 family member proteins to determine which proteins are O-GlcNAcylated under conditions of high HBP throughput, and how these proteins are associated with beta cell apoptosis. Eventually, we identified ten new O-GlcNAcylated proteins that were expressed during beta cell apoptosis, and analyzed the functional implications of these proteins in relation to pancreatic beta cell dysfunction.
MeSH terms
Acetylglucosamine/analogs & derivativesAcetylglucosamine/metabolismAcetylglucosamine/pharmacologyAnimalsApoptosis/drug effects*Apoptosis/physiologyCell LineDiabetes Mellitus, Type 2/etiologyDiabetes Mellitus, Type 2/metabolismGlucosamine/toxicityGlycosylation/drug effectsInsulin/secretionInsulin-Secreting Cells/cytologyInsulin-Secreting Cells/drug effects*Insulin-Secreting Cells/physiologyModels, BiologicalOximes/pharmacologyPhenylcarbamates/pharmacologyProteomicsProto-Oncogene Proteins c-akt/metabolismRatsSignal Transduction/drug effectsStreptozocin/toxicity
PMID
18047804
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
강, 엽
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