COBRE P3: ROLE OF HEXOSAMINE BIOSYNTHETIC PATHWAY AND POSTRANSLATIONAL O-GLCNAC

COBRE P3：己糖胺生物合成途径和翻译后 O-GLNAC 的作用

• 批准号: 8167765
• 负责人: Lauren Elizabeth Ball
• 金额: $ 15.38万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167765
• 关键词: Attenuated; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Enzymes; Event; Fibroblasts; Funding; Glucose; Goals; Grant; Hexosamines; Impaired wound healing; Impairment; Infection; Institution; Insulin; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Interstitial Collagenase; Modification; Nuclear Protein; Nuclear Proteins; O-GlcNAc transferase; Pathway interactions; Periodontal Ligament; Periodontium; Post-Translational Protein Processing; Receptor Signaling; Regulation; Research; Research Personnel; Resources; Role; Signal Pathway; Signal Transduction; Source; Testing; United States National Institutes of Health; diabetic patient; glycosylation; insulin signaling; macrophage; overexpression; peptide O-linked N-acetylglucosamine-beta-N-acetylglucosaminidase; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this project is to elucidate the role of posttranslational O-GlcNAc modification of protein Ser/Thr in the regulation of signal transduction events relevant to the complications associated with diabetes. We hypothesize that high glucose-induced elevation in O-GlcNAc glycosylation of cytoplasmic and/or nuclear proteins contributes to delayed healing of the periodontium and to the exaggerated response to infection observed in diabetic patients. Our first aim is to elucidate the mechanism by which O-GlcNAc modification of critical components of the insulin/IGF-1 receptor signaling pathways, IRS-1 and IRS-2, attenuates insulin signaling and to test the hypothesis that O-GlcNAc modification of these proteins attenuates IGF-1 receptor signaling. The second aim will test the hypothesis that IGF-1 signaling in periodontal ligament fibroblasts (PDLF) is attenuated by high glucose-induced O-GlcNAc modification. If this hypothesis is correct we anticipate that glucose-induced impairment of IGF-1 signaling may be alleviated by manipulation of the enzymes responsible for this modification, O-GlcNAcase and O-GlcNAc transferase. The third aim will determine whether the glucose-induced augmentation of LPS-stimulated secretion of MMP-1 from macrophages can be reduced by overexpression of the enzyme, O-GlcNAcase.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的长期目标是阐明蛋白质Ser/Thr的翻译后O-GLCNAC修饰在与糖尿病并发症相关的信号转导事件中的调节中的作用。 我们假设高葡萄糖诱导的细胞质和/或核蛋白的O-GLCNAC糖基化升高有助于延迟牙周愈合以及对糖尿病患者观察到的对感染的夸大反应。 我们的第一个目的是阐明胰岛素/IGF-1受体信号通路，IRS-1和IRS-2的O-GLCNAC修饰的O-GLCNAC修饰的机制，减轻胰岛素信号传导并测试这些蛋白质衰减IGF-1受体信号的O-GLCNAC修饰的假说。第二个目的将检验以下假设：牙周韧带成纤维细胞（PDLF）中的IGF-1信号传导通过高葡萄糖诱导的O-GLCNAC修饰减弱。 如果该假设是正确的，我们预计葡萄糖诱导的IGF-1信号传导的损伤可能会通过操纵负责这种修饰的酶，O-GlcNACase和O-GlCNAC转移酶来缓解。第三个目标将确定葡萄糖诱导的LPS刺激的MMP-1分泌是否可以通过酶O-Glcnacase的过表达来减少巨噬细胞的分泌。