通过脂酶C诱导的"酸性"基米林分解,TNF激活NF-kappa B
S Schütze1, K Potthoff, T Machleidt
1Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Germany.
Cell
|November 27, 1992
概括
瘤亡因子 (TNF) 通过脂途径激活转录因子NF-kappa B. 这涉及到米林分解为胺,由酸性米林酶触发,最终诱导NF-kappa B活性.
科学领域:
- 细胞信号通道是细胞信号通道.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 瘤亡因子 (TNF) 是炎症和免疫的关键细胞因子.
- 核转录因子kappa B (NF-kappa B) 的激活是TNF信号传输中的关键下游事件.
- 连接TNF与NF-kappa B激活的精确分子机制是复杂的,涉及多个信号分子.
研究的目的:
- 为了阐明调解TNF诱导的NF-kappa B激活的脂传播途径.
- 为了确定基酶 (SMase) 和基酶C (PC-PLC) 在这个信号级联中的作用.
- 提出一种胺生成模型及其对NF-kappaB的后续影响.
主要方法:
- 研究了髓 (SM) 分解和胺生成的作用.
- 使用了一种选择性PC特异性脂酶C (PC-PLC) 抑制剂 (D609).
- 在各种条件下评估NF-kappa B激活,包括异源PLC和合成二甲基甘油 (DAG) 在不同的pH水平下.
主要成果:
- 确定了一个信号通路,其中TNF-响应的PC-PLC产生1,2-二甲基甘油 (DAG).
- DAG的生成与一种酸性SM酶结合,导致髓 (SM) 的分解和胺的产生.
- 在pH值为5.0时观察到NF-kappa B激活,这意味着该途径中存在酸性SMase.
结论:
- 一个新的脂途径将TNF与NF-kappa B通过胺激活.
- 该途径涉及PC-PLC和酸性SMase的连续作用.
- 胺基生成是TNF快速诱导核NF-kappa B活性的一个关键步骤.
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