通过诱导细胞亡因子调解多聚 (ADP-ribose) 聚合酶-1-依赖细胞死亡
Seong-Woon Yu1, Hongmin Wang, Marc F Poitras
1Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Science (New York, N.Y.)
|July 13, 2002
概括
聚ADP-ribose) 聚合酶-1 (PARP-1) 通过信号诱导细胞灭绝因子 (AIF) 从线粒体释放,触发编程细胞死亡. 这种独立于酶的途径对于DNA损伤反应和细胞存活至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 在DNA损伤监测网络中,PARP-1对基因组保护至关重要.
- 此外,PARP-1 在缺血-再输液损伤,谷氨酸兴奋毒性和炎症状况后调解细胞死亡方面也发挥作用.
研究的目的:
- 阐明PARP-1在编程细胞死亡途径中的作用.
- 研究诱导亡因子 (AIF) 在PARP-1-介导的细胞死亡中的参与.
主要方法:
- 通过使用各种细胞死亡诱导剂,研究了PARP-1激活及其对诱导亡因子 (AIF) 转位的影响.
- 利用PARP抑制剂和PARP-1的遗传淘汰来评估细胞死亡机制.
- 采用抗体微注射来阻止AIF的功能.
主要成果:
- 激活PARP-1对于AIF从线粒体转移到细胞核至关重要.
- 对于PARP-1依赖的细胞死亡来说,AIF是必要的,这种细胞死亡被发现是独立于酶的.
- PARP 抑制剂和 PARP-1 基因淘汰阻止了 AIF 转位和随后的细胞死亡.
- 用抗体阻止AIF保护细胞免受PARP-1依赖的细胞毒性.
结论:
- PARP-1的激活启动了一个独立于酶的编程细胞死亡途径.
- 这一途径涉及AIF从线粒体释放的信号.
- PARP-1和AIF是细胞对DNA损伤和其他细胞毒性攻击反应的关键组成部分.
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