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Article: In vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes

TitleIn vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes
Authors
Issue Date1999
Citation
Journal of Immunology, 1999, v. 163, n. 9, p. 4909-4916 How to Cite?
AbstractCaspase-3 is essential for Fas-mediated apoptosis in vitro. We investigated the role of caspase-3 in Fas-mediated cell death in vivo by injecting caspase-3-deficient mice with agonistic anti-Fas Ab. Wild-type controls died rapidly of fulminant hepatitis, whereas the survival of caspase-3(-/-) mice was increased due to a delay in hepatocyte cell death. Bcl-2 expression in the liver was dramatically decreased in wild-type mice following anti-Fas injection, but was unchanged in caspase-3(-/-) mice. Hepatocytes from anti-Fas-injected wild-type, but not caspase-3(-/-), mice released cytochrome c into the cytoplasm. Western blotting confirmed the lack of caspase-3-mediated cleavage of Bcl-2. Presumably the presence of intact Bcl-2 in caspase-3(-/-) hepatocytes prevents the release of cytochrome c from the mitochondria, a required step for the mitochondrial death pathway. We also show by Western blot that Bcl-x(L), caspase-9, caspase-8, and Bid are processed by caspase-3 in injected wild-type mice but that this processing does not occur in caspase-3(-/-) mice. This study thus provides novel in vivo evidence that caspase-3, conventionally known for its downstream effector function in apoptosis, also modifies Bcl-2 and other upstream proteins involved in the regulation of Fas-mediated apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/291472
ISSN
2023 Impact Factor: 3.6
2023 SCImago Journal Rankings: 1.558
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWoo, Minna-
dc.contributor.authorHakem, Anne-
dc.contributor.authorElia, Andrew J.-
dc.contributor.authorHakem, Razqallah-
dc.contributor.authorDuncan, Gordon S.-
dc.contributor.authorPatterson, Bruce J.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:54:26Z-
dc.date.available2020-11-17T14:54:26Z-
dc.date.issued1999-
dc.identifier.citationJournal of Immunology, 1999, v. 163, n. 9, p. 4909-4916-
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/291472-
dc.description.abstractCaspase-3 is essential for Fas-mediated apoptosis in vitro. We investigated the role of caspase-3 in Fas-mediated cell death in vivo by injecting caspase-3-deficient mice with agonistic anti-Fas Ab. Wild-type controls died rapidly of fulminant hepatitis, whereas the survival of caspase-3(-/-) mice was increased due to a delay in hepatocyte cell death. Bcl-2 expression in the liver was dramatically decreased in wild-type mice following anti-Fas injection, but was unchanged in caspase-3(-/-) mice. Hepatocytes from anti-Fas-injected wild-type, but not caspase-3(-/-), mice released cytochrome c into the cytoplasm. Western blotting confirmed the lack of caspase-3-mediated cleavage of Bcl-2. Presumably the presence of intact Bcl-2 in caspase-3(-/-) hepatocytes prevents the release of cytochrome c from the mitochondria, a required step for the mitochondrial death pathway. We also show by Western blot that Bcl-x(L), caspase-9, caspase-8, and Bid are processed by caspase-3 in injected wild-type mice but that this processing does not occur in caspase-3(-/-) mice. This study thus provides novel in vivo evidence that caspase-3, conventionally known for its downstream effector function in apoptosis, also modifies Bcl-2 and other upstream proteins involved in the regulation of Fas-mediated apoptosis.-
dc.languageeng-
dc.relation.ispartofJournal of Immunology-
dc.titleIn vivo evidence that caspase-3 is required for Fas-mediated apoptosis of hepatocytes-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid10528193-
dc.identifier.scopuseid_2-s2.0-0032736175-
dc.identifier.volume163-
dc.identifier.issue9-
dc.identifier.spage4909-
dc.identifier.epage4916-
dc.identifier.isiWOS:000083256000037-
dc.identifier.issnl0022-1767-

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