SC COBRE: HUMAN ALKALINE CERAMIDASE REGULATION OF ANGIOGENESIS

SC COBRE：人体碱性神经酰胺酶对血管生成的调节

• 批准号: 7610445
• 负责人: CUNGUI MAO
• 金额: $ 6.87万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610445
• 关键词: Apoptosis; Blood Vessels; Blood capillaries; Ceramidase; Ceramides; Chronic; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetic Retinopathy; Endothelial Cells; Enzymes; Family; Funding; G-Protein-Coupled Receptors; Grant; Growth; Growth Factor; Human; Hydrolysis; Inflammation; Institution; Intervention; Lead; Lipids; Mediating; Metabolism; Object Attachment; Organ; Pathology; Play; Process; Regulation; Research; Research Personnel; Resources; Rheumatoid Arthritis; Role; Solid Neoplasm; Source; Sphingolipids; Sphingosine; Sphingosine-1-Phosphate Receptor; Time; Tumor Angiogenesis; United States National Institutes of Health; Wound Healing; analog; angiogenesis; capillary; chemokine; cytokine; inhibitor/antagonist; Apoptosis; Blood Vessels; Blood capillaries; Ceramidase; Ceramides; Chronic; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetic Retinopathy; Endothelial Cells; Enzymes; Family; Funding; G-Protein-Coupled Receptors; Grant; Growth; Growth Factor; Human; Hydrolysis; Inflammation; Institution; Intervention; Lead; Lipids; Mediating; Metabolism; Object Attachment; Organ; Pathology; Play; Process; Regulation; Research; Research Personnel; Resources; Rheumatoid Arthritis; Role; Solid Neoplasm; Source; Sphingolipids; Sphingosine; Sphingosine-1-Phosphate Receptor; Time; Tumor Angiogenesis; United States National Institutes of Health; Wound Healing; analog; angiogenesis; capillary; chemokine; cytokine; inhibitor/antagonist

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. Angiogenesis, the process of formation of new capillaries from preexisting blood vessels, is essential for the proper organ development and tissue repair. However, uncontrollable angiogenesis may lead to pathologies such as chronic inflammation, diabetic retinopathy, rheumatoid arthritis, and growth of solid tumors. Angiogenesis is coordinately regulated by cytokines, chemokines, growth factors, and inhibitors. In addition to these proteinaceous factors, several lipid factors have been shown to play an important role in mediating angiogenesis. Prominent among them are sphingosine-1-P (S1P) and its analogs which potentiates growth factor-induced angiogenesis by bonding to G protein coupled receptors of the Edg receptor family. S1P is a metabolite of sphingolipids. It is generated from sphingosine through the action of sphingosine kianse. Sphingosine in turn is generated from hydrolysis of ceramide through the action of ceramidases. More recently, several studies demonstrate that ceramide induces growth arrest and apoptosis of endothelial cells. These results suggest that regulation of metabolism of sphingolipids may control angiogenesis. Our results for the first time demonstrate that the human alkaline phytoceramidase is a key enzyme that regulates the levels of ceramides and the analog of S1P, dihdyrosphingosine-1-P. This establishes the human alkaline phytoceramidase as a potential target for chemotherapeutic interventions of tumor angiogenesis and growth.

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。 血管生成是由先前存在的血管形成新毛细血管的过程，对于适当的器官发育和组织修复至关重要。然而，无法控制的血管生成可能导致诸如慢性炎症，糖尿病性视网膜病，类风湿关节炎和实体瘤生长等病理。血管生成由细胞因子，趋化因子，生长因子和抑制剂协同调节。除了这些蛋白质因子外，已经证明几种脂质因子在介导血管生成中起着重要作用。其中突出的是鞘氨醇-1-P（S1P）及其类似物，它们通过与EDG受体家族的G蛋白偶联受体键键结合来增强生长因子诱导的血管生成。 S1P是鞘脂的代谢物。它是从鞘氨醇通过鞘氨醇的作用而产生的。鞘氨酸反过来是由神经酰胺通过神经酶的作用而产生的。最近，一些研究表明，神经酰胺诱导内皮细胞的生长停滞和凋亡。这些结果表明，调节鞘脂的代谢可能控制血管生成。我们的结果首次证明了人类碱性植物酰胺酶是一种关键酶，可调节神经酰胺的水平和S1P的类似物，二氢磷酶氨酸-1-P。这确立了人类碱性植物酰胺酶，作为肿瘤血管生成和生长的化学治疗干预措施的潜在靶标。