Abstract
The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. We generated mice deficient in the two effectors, caspase 3 and caspase 7, which died immediately after birth with defects in cardiac development. Fibroblasts lacking both enzymes were highly resistant to both mitochondrial and death receptor-mediated apoptosis, displayed preservation of mitochondrial membrane potential, and had defective nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Inducing Factor / metabolism
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Apoptosis*
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Caspase 3
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Caspase 7
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Caspases / deficiency
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Caspases / metabolism*
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Cell Nucleus / metabolism
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Cell Shape
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Cell Survival
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Cells, Cultured
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Cytochromes c / metabolism
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DNA Fragmentation
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Female
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Fibroblasts / cytology
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Heart / embryology
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Heart Defects, Congenital / etiology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondria / metabolism
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Mitochondria / physiology*
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Mitochondrial Membranes / physiology
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Permeability
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T-Lymphocytes / cytology
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bcl-2-Associated X Protein / metabolism
Substances
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Apoptosis Inducing Factor
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AIFM1 protein, mouse
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bcl-2-Associated X Protein
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Cytochromes c
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Casp3 protein, mouse
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Casp7 protein, mouse
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Caspase 3
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Caspase 7
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Caspases