在体内apoptotic途径中对caspase 9的差异性要求 in vivo
1Amgen Institute, Toronto, Ontario, Canada.
Cell
|August 26, 1998
概括
卡斯帕酶9 (Casp9) 突变通过阻断亡,导致胚胎致死性和大脑发育受损. 研究表明,Casp9在细胞染色体c的下游作用,突出至少有四种不同的哺乳动物细胞亡途径.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 卡斯帕酶9 (Casp9) 对于细胞亡至关重要,这是一个被编程的细胞死亡过程.
- Casp9 缺乏导致胚胎死亡和发育缺陷,特别是在大脑中.
- 了解Casp9的作用对于破译亡途径及其对发育的影响至关重要.
研究的目的:
- 调查卡斯帕斯9在各种亡刺激中的精确作用.
- 为了确定Casp9在阿波子级联中的位置,特别是与细胞染色体c的关系.
- 为了阐明哺乳动物细胞中亡途径的多样性.
主要方法:
- 使用Caspase 9淘汰 (Casp9-/-) 胚胎干细胞,纤维细胞和胸细胞.
- 突变细胞暴露于各种亡诱导物,如紫外线辐射,玛辐射,德克萨米他和抗CD95抗体.
- 评估了亡耐药性,线粒体膜潜力,细胞染色体c释放和卡斯帕酶处理.
主要成果:
- 卡斯普9-/-细胞对紫外线,玛辐射和甲诱导的亡具有抗性,但对抗CD95.5具有敏感性.
- 线粒体膜潜能被保留在Casp9-/-细胞中,并且在UV刺激时细胞染色体c转移到细胞质中.
- 在Casp9-/- ES细胞中抑制了卡斯帕酶处理,这表明Casp9作用于细胞染色体c的下游.
- 不同细胞类型的明显的亡反应表明了多种途径.
结论:
- 卡斯帕酶9在多种亡途径中发挥着关键作用,作用于细胞染色体c的下游.
- 该研究根据Casp9和Casp3的要求在哺乳动物细胞中确定了至少四种不同的亡途径.
- 这些发现加深了我们对亡调节及其对发育和疾病的影响的理解.
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