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KMID : 0380220070400061058
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Journal of Biochemistry and Molecular Biology
2007 Volume.40 No. 6 p.1058 ~ p.1068
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Proteomic Analysis of O-GlcNAc Modifications Derived from Streptozotocin and Glucosamine Induced &bgr;-cell Apoptosis
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Park Jungeun
Kwon Hyejin
Kang Yup
Kim Youngsoo
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Abstract
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The post-translational modifications of Ser and Thr residues by O-linked &bgr;-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 &bgr; cell dysfunction, we increased nucleocytoplasmic protein O-GlcNAcylation levels in &bgr; 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 &bgr; cells. This observed &bgr; 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 &bgr; cell apoptosis. Eventually, we identified ten new O-GlcNAcylated proteins that were expressed during &bgr; cell apoptosis, and analyzed the functional implications of these proteins in relation to pancreatic &bgr; cell dysfunction.
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KEYWORD
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Hexosamine biosynthetic pathway, O-glycosylation, Proteomics, &bgr, cell apoptosis
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