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

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 血管生成是从原有血管形成新毛细血管的过程，对于器官的正常发育和组织修复至关重要。然而，不可控制的血管生成可能导致病理学，如慢性炎症、糖尿病视网膜病变、类风湿性关节炎和实体瘤的生长。血管生成受细胞因子、趋化因子、生长因子和抑制剂的协同调节。除了这些蛋白质因子外，几种脂质因子已被证明在介导血管生成中起重要作用。其中突出的是鞘氨醇-1-P（S1P）及其类似物，其通过与Edg受体家族的G蛋白偶联受体结合来增强生长因子诱导的血管生成。S1P是鞘脂的代谢产物。它是由鞘氨醇通过鞘氨醇激酶的作用产生的。鞘氨醇又通过神经酰胺酶的作用由神经酰胺水解产生。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，调节鞘脂代谢可能控制血管生成。我们的研究结果首次表明，人类碱性植物神经酰胺酶是一种关键酶，调节神经酰胺和类似物的S1P，二氢鞘氨醇-1-P的水平。这建立了人类碱性植物神经酰胺酶作为一个潜在的目标化疗干预肿瘤血管生成和生长。