Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms
Nitric oxide donors, nitrosothiols and mitochondrial respiration inhibitors induce caspase activation by different mechanisms
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DOI：
10.1016/s0014-5793(00)01140-6
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发表时间：
2000-02-11
期刊：
影响因子：
3.5
通讯作者：
Brown, GC
中科院分区：
文献类型：
--
作者：
Borutaite, V;Morkuniene, R;Brown, GC
我们研究了不同类型的NO供体通过打开线粒体通透性过渡孔（PTP）或抑制线粒体呼吸在多大程度上诱导caspase激活。我们发现亚硝基硫醇可以直接打开离体线粒体的PTP并引起细胞色素c的释放，而NONOate供体则不能。在巨噬细胞中，亚硝基硫醇引起的半胱天冬酶激活可被环孢素A或钙螯合所阻断，这两种物质均可阻止PTP打开，而NONOates引起的半胱天冬酶激活对这些药物的敏感性要低得多。线粒体呼吸抑制剂不能促进离体线粒体中PTP的打开，尽管它们在巨噬细胞中引起caspase的激活，但这种激活比NO供体引起的激活要慢，并且对环孢素和钙螯合剂相对不敏感，表明PTP的打开无关。(C) 2000年欧洲生化学会联合会。
We investigated to what extent different types of NO donors induce caspase activation by opening of the mitochondrial permeability transition pore (PTP) or inhibition of mitochondrial respiration. We found that nitrosothiols can directly open the PTP in isolated mitochondria and cause cytochrome c release, whereas NONOate donors can not. In macrophages nitrosothiols cause caspase activation that is blocked by cyclosporin A or calcium chelation, both of which prevent PTP opening, whereas caspase activation caused by NONOates is much less sensitive to these agents. Inhibitors of mitochondrial respiration did not promote PTP opening in isolated mitochondria, and although they cause caspase activation in macrophages, this activation was slower than that caused by NO donors, and was relatively insensitive to cyclosporin and calcium chelators suggesting that PTP opening was not involved. (C) 2000 Federation of European Biochemical Societies.