Nur-E-Kamal Alam, Gross Stephane R, Pan Zui, Balklava Zita, Ma Jianjie, Liu Leroy F
Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
J Biol Chem. 2004 Jun 11;279(24):24911-4. doi: 10.1074/jbc.C400051200. Epub 2004 Apr 8.
Release of cytochrome c from mitochondria is a major event during apoptosis. Released cytochrome c has been shown to activate caspase-dependent apoptotic signals. In this report, we provide evidence for a novel role of cytochrome c in caspase-independent nuclear apoptosis. We showed that cytochrome c, released from mitochondria upon apoptosis induction, gradually accumulates in the nucleus as evidenced by both immunofluorescence and subcellular fractionation. Parallel to nuclear accumulation of cytochrome c, acetylated histone H2A, but not unmodified H2A, was released from the nucleus to the cytoplasm. Addition of purified cytochrome c to isolated nuclei recapitulated the preferential release of acetylated, but not deacetylated, histone H2A. Cytochrome c was also found to induce chromatin condensation. These results suggest that the nuclear accumulation of cytochrome c may be directly involved in the remodeling of chromatin. Our results provide evidence of a novel role for cytochrome c in inducing nuclear apoptosis.
细胞色素c从线粒体释放是细胞凋亡过程中的一个主要事件。已证实释放的细胞色素c可激活半胱天冬酶依赖性凋亡信号。在本报告中，我们提供了细胞色素c在非半胱天冬酶依赖性核凋亡中的新作用的证据。我们发现，在诱导凋亡时从线粒体释放的细胞色素c会逐渐在细胞核中积累，免疫荧光和亚细胞分级分离均证明了这一点。与细胞色素c在细胞核中的积累同时发生的是，乙酰化组蛋白H2A而非未修饰的H2A从细胞核释放到细胞质中。将纯化的细胞色素c添加到分离的细胞核中可重现乙酰化而非去乙酰化组蛋白H2A的优先释放。还发现细胞色素c可诱导染色质浓缩。这些结果表明，细胞色素c在细胞核中的积累可能直接参与染色质重塑。我们的结果提供了细胞色素c在诱导核凋亡中的新作用的证据。
