The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Cathepsin B contributes to TNF-α–mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c
Open accessAbstract
TNF-alpha-induced apoptosis is thought to involve mediators from acidic vesicles. Cathepsin B (cat B), a lysosomal cysteine protease, has recently been implicated in apoptosis. To determine whether cat B contributes to TNF-alpha-induced apoptosis, we exposed mouse hepatocytes to the cytokine in vitro and in vivo. Isolated hepatocytes treated with TNF-alpha in the presence of the transcription inhibitor actinomycin D (AcD) accumulated cat B in their cytosol. Further experiments using cell-free systems indicated that caspase-8 caused release of active cat B from purified lysosomes and that cat B, in turn, increased cytosol-induced release of cytochrome c from mitochondria. Consistent with these observations, the ability of TNF-alpha/AcD to induce mitochondrial release of cytochrome c, caspase activation, and apoptosis of isolated hepatocytes was markedly diminished in cells from CatB(-/-) mice. Deletion of the CatB gene resulted in diminished liver injury and enhanced survival after treatment in vivo with TNF-alpha and an adenovirus construct expressing the IkappaB superrepressor. Collectively, these observations suggest that caspase-mediated release of cat B from lysosomes enhances mitochondrial release of cytochrome c and subsequent caspase activation in TNF-alpha-treated hepatocytes.
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Cites
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Cited by
Organelle-specific initiation of cell death pathways
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Free Fatty Acids Induce JNK-dependent Hepatocyte Lipoapoptosis
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Self-citationCysteine cathepsin proteases: regulators of cancer progression and therapeutic response
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Metadata
- Authors
- Guicciardi, M. E., Deussing, J., Miyoshi, H., Bronk, S. F., Svingen, P. A., Peters, C., Kaufmann, S. H., & Gores, G. J.
- Venue
- Journal of Clinical Investigation
- Published
- 2000-11-01
- Volume
- 106
- Issue
- 9
- Pages
- 1127-1137
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2134388096
- Cited by
- 710
- References
- 64
- FWCI
- 12.73
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Guicciardi, M. E., Deussing, J., Miyoshi, H., Bronk, S. F., Svingen, P. A., Peters, C., Kaufmann, S. H., & Gores, G. J. (2000). Cathepsin B contributes to TNF-α–mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. Journal of Clinical Investigation. https://doi.org/10.1172/jci9914
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