REACTIVE OXYGEN SPECIES AS MEDIATORS OF TGF-B1 ACTIONS

活性氧作为 TGF-B1 作用的介体

• 批准号: 6043673
• 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/6043673
• 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 （摘自申请人摘要）这是一份申请， 为维克托J. Thannickal博士提供额外的研究培训， 完成一个项目，这将使他有竞争力， 独立支持。 他现在已经花了两年的时间进行研究训练， 在此期间，他发现了一种新的NADH的存在， 氧化酶在某些细胞表面，包括成纤维细胞， 在肺纤维化的发展中起重要作用。 而且他 发现这种酶受TGF-β 1刺激，TGF-β 1是一种细胞因子， 与纤维化有关，并且能够增强 巨噬细胞化学引诱物的产生和 TGF-B1本身可能使该过程永久化。 他认为， TGF-B1刺激H2 O2产生可能是细胞内的信号传导事件。 纤维化过程，并希望进一步评估这一研究设计 目的：1）评估NADH氧化酶的酶性质; 2）评估 通过蛋白酪氨酸的研究可能的相关转导途径 磷酸化;和3）确定与可能的转录的关联 激活M-CSF和TGF-β 1基因的途径。 巴里范伯格医生会 继续赞助和监督他的工作。 除了日常的 由B博士指导的研究。范伯格和坦尼克尔博士将审查他的 与包括Norman Krinsky博士、欧文博士在内的委员会合作， 塔夫茨大学医学院的阿里亚斯和布伦特科克伦以及威尔 在邻近的萨克勒研究生院（Sackler Graduate School of the 塔夫茨大学医学院。