Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2007-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319343208 |
| _version_ | 1818854501119950848 |
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| author | Hiroshi Kawai Takuo Suzuki Tetsu Kobayashi Akiko Ishii-Watabe Haruna Sakurai Hisayuki Ohata Kazuo Honda Kazutaka Momose Takao Hayakawa Toru Kawanishi |
| author_facet | Hiroshi Kawai Takuo Suzuki Tetsu Kobayashi Akiko Ishii-Watabe Haruna Sakurai Hisayuki Ohata Kazuo Honda Kazutaka Momose Takao Hayakawa Toru Kawanishi |
| author_sort | Hiroshi Kawai |
| collection | DOAJ |
| description | 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. Keywords:: tumor necrosis factor (TNF)-α, cytochrome c, mitochondrial depolarization, caspase, real-time imaging |
| first_indexed | 2024-12-19T07:53:42Z |
| format | Article |
| id | doaj.art-5204b19b73cb489da5b4d138021a2fec |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-19T07:53:42Z |
| publishDate | 2007-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-5204b19b73cb489da5b4d138021a2fec2022-12-21T20:30:04ZengElsevierJournal of Pharmacological Sciences1347-86132007-01-011032159167Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell DeathHiroshi Kawai0Takuo Suzuki1Tetsu Kobayashi2Akiko Ishii-Watabe3Haruna Sakurai4Hisayuki Ohata5Kazuo Honda6Kazutaka Momose7Takao Hayakawa8Toru Kawanishi9Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, Japan; Faculty of Pharmaceutical Sciences, Josai International University, Chiba 283-8555, Japan; Corresponding author (affiliation #3). hkawai@jiu.ac.jpDivision of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, JapanDivision of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, JapanDivision of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, JapanDepartment of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo 142-8555, JapanDivision of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, JapanDivision of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, Japan; Present affiliation: Division of Drugs, National Institute of Health Sciences, Tokyo 158-8501, JapanThe 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. Keywords:: tumor necrosis factor (TNF)-α, cytochrome c, mitochondrial depolarization, caspase, real-time imaginghttp://www.sciencedirect.com/science/article/pii/S1347861319343208 |
| spellingShingle | Hiroshi Kawai Takuo Suzuki Tetsu Kobayashi Akiko Ishii-Watabe Haruna Sakurai Hisayuki Ohata Kazuo Honda Kazutaka Momose Takao Hayakawa Toru Kawanishi Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death Journal of Pharmacological Sciences |
| title | Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death |
| title_full | Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death |
| title_fullStr | Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death |
| title_full_unstemmed | Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death |
| title_short | Caspase Cascade Proceeds Rapidly After Cytochrome c Release From Mitochondria in Tumor Necrosis Factor-α-Induced Cell Death |
| title_sort | caspase cascade proceeds rapidly after cytochrome c release from mitochondria in tumor necrosis factor α induced cell death |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319343208 |
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