Altered Apoptotic Responses in Chemically-Resistant Mammalian Cell Variants

耐化学性哺乳动物细胞变体中细胞凋亡反应的改变

• 批准号: 9630362
• 负责人: James Wyche
• 金额: $ 30万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9630362&HistoricalAwards=false
• 关键词: Altered; Apoptotic; Responses; Chemically; Resistant

96-30362 Wyche Programmed cell death is a normal part of animal development, is actively controlled by specific gene products, and is an event that occurs in various cells in the embryo and in adults. Programmed cell death, or apoptosis, can be induced in various cultured cell types by chemical and by physical treatment. Yet little is known about the molecular mechanism of apoptosis. This is partly caused by the fact that the positive and negative regulators of apoptosis are as yet unknown and partly to the lack of suitable mutants in the apoptotic signaling pathway. The objectives of this proposal are: a) isolation of chemically-resistant apoptosis cell variants from a human cell line (HL-60) and classification of the variants into complementation groups; b) identification of sequential cellular changes, structurally and biochemically, that are specifically associated with early progression of chemically-induced cell apoptosis; d) characterization of specific events leading to the activation of proteases as well as alterations in protein and DNA target sites in apoptotic cells and their variants. These studies should lead to the construction of the apoptotic signaling pathway and to insights into the relationship between apoptosis regulatory gene products and to specific events in the apoptotic signaling pathway. %%% Programmed cell death is a normal part of animal development, is actively controlled by specific gene products, and is an event that occurs in various cells in the embryo and in adults. Programmed cell death, or apoptosis, can be induced in various cultured cell types by chemical and by physical treatment. Yet little is known about the molecular mechanism of apoptosis. ***

96-30362 Wyche程序性细胞死亡是动物发育的正常部分，由特定的基因产物主动控制，是发生在胚胎和成人的各种细胞中的事件。细胞程序性死亡，或称细胞凋亡，可以通过化学和物理处理在各种培养细胞中诱导。然而，人们对细胞凋亡的分子机制知之甚少。这部分是由于目前尚不清楚细胞凋亡的正向和负向调控因子，部分原因是在细胞凋亡信号通路中缺乏合适的突变体。这项建议的目标是：a)从人类细胞系(HL-60)中分离耐药的凋亡细胞变体，并将这些变体分类为互补组；b)确定在结构和生物化学上与化学诱导的细胞凋亡的早期进展特别相关的连续细胞变化；d)表征导致蛋白水解酶激活的特定事件以及凋亡细胞及其变体中蛋白质和DNA靶点的变化。这些研究将有助于构建细胞凋亡信号通路，并深入了解细胞凋亡调控基因产物与细胞凋亡信号通路中特定事件之间的关系。程序性细胞死亡是动物发育的正常部分，由特定的基因产物主动控制，是发生在胚胎和成人的各种细胞中的事件。细胞程序性死亡，或称细胞凋亡，可以通过化学和物理处理在各种培养细胞中诱导。然而，人们对细胞凋亡的分子机制知之甚少。***