REACTIVE OXYGEN SPECIES AS MEDIATORS OF TGF-B1 ACTIONS

活性氧作为 TGF-B1 作用的介体

• 批准号: 6182678
• 负责人: Victor J. Thannickal
• 金额: $ 11.35万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182678
• 关键词: NAD(P)H dehydrogenase; biological signal transduction; colony stimulating factor; enzyme activity; enzyme induction /repression; enzyme mechanism; free radical oxygen; gene induction /repression; genetic transcription; hydrogen peroxide; molecular pathology; nuclear factor kappa beta; oxidative stress; phosphorylation; pulmonary fibrosis /granuloma; tissue /cell culture; transforming growth factors

DESCRIPTION (Adapted from the applicant's abstract) This is an application for additional research training for Dr. Victor J. Thannickal while he pursues accomplishment of a project that will allow him to be competitive for independent support. He has now spent two years in a research training fellowship, during which time he has identified the presence of a novel NADH oxidase on certain cell surfaces including that of the fibroblast which is important in the development of pulmonary fibrosis. Furthermore, he has found that this enzyme is stimulated by TGF-Bl, a cytokine whose presence has been associated with fibrosis and which is capable of enhancing the production of a macrophage chemoattractant and the autocrine production of TGF-B1 itself which may perpetuate the process. He theorizes that stimulation of H202 production by TGF-B1 may be a signaling event in the fibrotic process and wishes to evaluate this further with studies designed to: 1) assess enzymatic properties of the NADH oxidase; 2) evaluate possible related transduction pathways through studies of protein tyrosine phosphorylation; and 3) determine association with possible transcription pathways that activate M-CSF and TGF-B1 genes. Dr. Barry Fanburg will continue to sponsor and supervise his work. In addition to the daily mentored research by Dr. B. Fanburg and Dr. Thannickal will review his progress quarterly with a committee that includes Drs. Norman Krinsky, Irwin Arias and Brent Cochran of the Tufts University School of Medicine and will take relevant course work at the adjacent Sackler Graduate School of the Tufts University School of Medicine.

描述 （改编自申请人的摘要）这是一份申请 Victor J. Thannickal 博士在攻读博士学位期间接受了额外的研究培训 完成一个项目将使他在竞争中具有竞争力 独立支持。 他现在已经接受了两年的研究培训 奖学金期间，他发现了一种新型 NADH 的存在 某些细胞表面的氧化酶，包括成纤维细胞的氧化酶 在肺纤维化的发生发展中具有重要意义。 此外，他还有 发现这种酶受到 TGF-Bl 的刺激，TGF-Bl 是一种细胞因子，其存在 与纤维化有关，并且能够增强 巨噬细胞趋化剂的产生和自分泌 TGF-B1 本身可以使该过程持续下去。 他的理论认为 TGF-B1 刺激 H2O2 产生可能是 纤维化过程并希望通过设计的研究进一步评估这一点 目的： 1) 评估 NADH 氧化酶的酶学特性； 2）评估 通过研究蛋白质酪氨酸可能相关的转导途径 磷酸化； 3) 确定与可能的转录的关联 激活 M-CSF 和 TGF-B1 基因的途径。 巴里·范伯格博士将 继续赞助和监督他的工作。 除了日常 B. Fanburg 博士和 Thannickal 博士指导的研究将回顾他的研究 与包括博士在内的委员会每季度取得进展。诺曼·克林斯基、欧文 塔夫茨大学医学院的阿里亚斯和布伦特·科克伦将 在邻近的萨克勒研究生院学习相关课程 塔夫茨大学医学院。