Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death

Journal of Pharmacological Sciences

Tetsu Kobayashi¹  Kazutaka Momose²  Takuo Suzuki¹  Kazuo Honda²  Akiko Ishii-Watabe¹  Takao Hayakawa¹  Toru Kawanishi¹  Hiroshi Kawai¹  Haruna Sakurai²  Hisayuki Ohata² 

[1] Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Japan;Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Japan

关键词: tumor necrosis factor (TNF)-α;    cytochrome c;    mitochondrial depolarization;    caspase;    real-time imaging;   

DOI  :  10.1254/jphs.FP0060877

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(4)The caspase activation cascade and mitochondrial changes are major biochemical reactions in the apoptotic cell death machinery. We attempted to clarify the temporal relationship between caspase activation, cytochrome c release, mitochondrial depolarization, and morphological changes that take place during tumor necrosis factor (TNF)-α-induced cell death in HeLa cells. These reactions were analyzed at the single-cell level with 0.5 – 1 min resolution by using green fluorescent protein (GFP)-variant-derived probes and chemical probes. Cytochrome c release, caspase activation, and cellular shrinkage were always observed in this order within 10 min in all dying cells. This sequence of events was thus considered a critical pathway of cell death. Mitochondrial depolarization was also observed in all dying cells observed, but frequently occurred after caspase activation and cellular shrinkage. Mitochondrial depolarization is therefore likely to be a reaction that does not induce caspase activation and subsequent cellular shrinkage. Mitochondrial changes are important for apoptotic cell death; moreover, cytochrome c release, and not depolarization, is a key reaction related to cell death. In addition, we also found that the apoptotic pathway proceeds only when cells are exposed to TNF-α. These findings suggest that the entire cell death process proceeds rapidly during TNF-α exposure.

【 授权许可】

Unknown