REGULATORY MECHANISMS OF APOPTOTIC CELL DEATH

调节细胞对凋亡刺激敏感性的机制有 人们对此知之甚少。大量数据表明，活性氧 中间体(R01)可能在这方面发挥关键作用。为 例如，PI已经证明细胞内02-增加- 似乎可以保护细胞免受Fas介导的死亡。在这项提案中， PI计划：1)使用各种药物改变细胞内02-产生 在各种不同类型的细胞中被刺激死亡，因此 可以确定这个观察的概括性；2)检查 氧化还原平衡对半胱氨酸天冬氨酸氨基转移酶活性的影响；3)确定Bcl2是否改变 细胞内氧化还原状态；4)评估氧化还原状态改变对 体内肿瘤细胞的凋亡敏感性；以及5)决定是否 淋巴细胞对凋亡敏感性的活化相关变化 刺激依赖于氧化还原状态。

The mechanisms that mediate cellular sensitivity to apoptotic stimuli are poorly understood. Considerable data suggests that reactive oxygen intermediates (R01s) may play a critical role in this regard. For example, the PI has demonstrated that increases in intracellular 02- appears to protect cells from Fas-mediated death. In this proposal, the PI plans to: 1) use various agents to alter intracellular 02- production in a variety of different cells types stimulated to die so that the generalizability of this observation can determined; 2) examine the effects of redox balance on caspase activity; 3) determine if Bcl-2 alters redox state in cells; 4) evaluate the effects of altered redox state on apoptosis sensitivity of tumor cells in vivo; and 5) determine if activation-associated changes in lymphocyte sensitivity to apoptotic stimuli is redox state dependent.