PROGRAMMED CELL DEATH IN THE NERVOUS SYSTEM

神经系统中的程序性细胞死亡

• 批准号: 6290657
• 负责人: RICHARD J. YOULE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290657
• 关键词: T lymphocyte; apoptosis; cell growth regulation; cytotoxicity; developmental immunology; developmental neurobiology; heterokaryon; human subject; human tissue; methylphenyltetrahydropyridine; monoclonal antibody; neuroprotectants; neurotoxins; tissue /cell culture

We have studied programmed cell death in the nervous system and the biochemical mechanism of apoptosis in general. (1) To analyze apoptosis in the nervous system we developed a new method to identify apoptotic cells under the microscope. This new method allowed us to identify apoptosis as the method of cerebellar granule cell death during development and after MPP+ treatment. (2) We have developed monoclonal antibodies against apoptosis regulatory proteins Bcl-2, Bcl-x, and Bax to probe their mechanism of action in vitro and in vivo. The antibodies reveal that Bax migrates from the cytosol to cell membranes during apoposis. (4) To explore Bax, Bcl-2 and Bcl-xl movement in neurons the green flourescent protein has been used to tag and follow the proteins during apoptosis. We discovered that Bax and Bcl-xl move from the cytosol to the mitochendria as an essential step in their mechanism of apoptosis control. (5) We found RNase L to mediate virus and interferon-induced apoptosis. (6) We developed a new way to block cell apoptosis by delivery of Bcl-x to the cell surface. - programmed cell death; nervous system; apoptosis; Bcl-2

我们研究了神经系统中的程序性细胞死亡和细胞凋亡的生化机制。(1)为了分析神经系统中的细胞凋亡，我们开发了一种新的方法，在显微镜下鉴定凋亡细胞。这种新的方法使我们能够确定细胞凋亡的方法小脑颗粒细胞死亡过程中的发展和MPP+处理后。(2)我们已经开发了抗凋亡调节蛋白Bcl-2，Bcl-x和Bax的单克隆抗体，以探测它们在体外和体内的作用机制。抗体显示Bax在凋亡过程中从细胞质迁移到细胞膜。(4)为了探索Bax、Bcl-2和Bcl-xl在神经元中的运动，已经使用绿色荧光蛋白来标记和跟踪凋亡过程中的蛋白。我们发现Bax和Bcl-xl从胞质溶胶移动到线粒体作为其细胞凋亡控制机制中的重要步骤。(5)我们发现RNase L介导病毒和干扰素诱导的细胞凋亡。(6)我们开发了一种通过将Bcl-x递送到细胞表面来阻断细胞凋亡的新方法。- 程序性细胞死亡;神经系统;凋亡; Bcl-2