{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360016870028047744.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.4049/jimmunol.153.4.1778"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jimmunol/article-pdf/153/4/1778/62396512/1778.pdf"}}],"dc:title":[{"@value":"Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-\n                    <i>alpha</i>\n                    requires transcriptional arrest."}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Freshly isolated mouse hepatocytes were essentially insensitive to TNF-alpha cytotoxicity. However, TNF-alpha induced a concentration-dependent cell death in hepatocytes that had been pretreated with the transcriptional inhibitors actinomycin D (ActD), D-galactosamine, or alpha-amanitin. Unlike RNA synthesis inhibition, a translational block in the presence of cycloheximide (CHX) or puromycin did not sensitive hepatocytes to TNF. On the contrary, these agents prevented hepatocytotoxicity induced by ActD/TNF. Pretreatment with peroxides or glutathione depletors had no significant influence on TNF cytotoxicity. In vivo treatment of mice with ActD/TNF caused hepatic failure, which was significantly reduced by co-treatment with CHX. These findings demonstrate that protein synthesis is required for this mechanism of cell death. To test whether TNF may trigger an endogenous suicide program in hepatocytes, we examined whether DNA fragmentation preceded cell death. In the culture system, hepatocellular DNA fragmentation in the presence of ActD/TNF was observed several hours before lactate dehydrogenase release and was inhibited by CHX. Similar results were obtained in vivo. Chromatin condensation and the formation of apoptotic bodies were observed in livers from mice treated with ActD/TNF and significant DNA fragmentation was detected as early as 4 h after challenge. At this time, organ total glutathione content and plasma transaminase levels were not significantly different from those of untreated controls. The findings of this study demonstrate that direct hepatotoxicity of TNF-alpha is associated with an apoptotic mechanism that becomes manifest under the metabolic condition of arrested transcription and functional translation.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380016870028047745","@type":"Researcher","foaf:name":[{"@value":"M Leist"}],"jpcoar:affiliationName":[{"@value":"Biochemical Pharmacology, Faculty of Biology, University of Konstanz , Konstanz ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016870028047748","@type":"Researcher","foaf:name":[{"@value":"F Gantner"}],"jpcoar:affiliationName":[{"@value":"Biochemical Pharmacology, Faculty of Biology, University of Konstanz , Konstanz ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016870028047746","@type":"Researcher","foaf:name":[{"@value":"I Bohlinger"}],"jpcoar:affiliationName":[{"@value":"Biochemical Pharmacology, Faculty of Biology, University of Konstanz , Konstanz ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016870028047747","@type":"Researcher","foaf:name":[{"@value":"P G Germann"}],"jpcoar:affiliationName":[{"@value":"Institute of Pathology and Toxicology Byk Gulden , Hamburg ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016870028047744","@type":"Researcher","foaf:name":[{"@value":"G Tiegs"}],"jpcoar:affiliationName":[{"@value":"Biochemical Pharmacology, Faculty of Biology, University of Konstanz , Konstanz ,"}]},{"@id":"https://cir.nii.ac.jp/crid/1380016870028047616","@type":"Researcher","foaf:name":[{"@value":"A Wendel"}],"jpcoar:affiliationName":[{"@value":"Biochemical Pharmacology, Faculty of Biology, University of Konstanz , Konstanz ,"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221767"},{"@type":"EISSN","@value":"15506606"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00221767"}],"prism:publicationName":[{"@value":"The Journal of Immunology"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"1994-08","prism:volume":"153","prism:number":"4","prism:startingPage":"1778","prism:endingPage":"1788"},"reviewed":"false","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/jimmunol/article-pdf/153/4/1778/62396512/1778.pdf"}],"createdAt":"2022-12-31","modifiedAt":"2026-02-09","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002214555198976","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Interferon-gamma–mediated tissue factor expression contributes to T-cell-mediated hepatitis through induction of hypercoagulation in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004236730128128","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Low susceptibility of NC/Nga mice to the lipopolysaccharide-mediated lethality with <scp>d</scp>-galactosamine sensitization and the involvement of fewer natural killer T cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285712541111424","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"DNA Methyltransferase Inhibitor Zebularine Induces Human Cholangiocarcinoma Cell Death through Alteration of DNA Methylation Status"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204286894208","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Effect of Gadolinium Chloride Treatment on Concanavalin A-Induced Cytokine mRNA Expression in Mouse Liver."},{"@language":"ja-Kana","@value":"Effect of Gadolinium Chloride Treatment"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204414993280","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Aggravation of Galactosamine Hepatotoxicity by Albumin in Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204625152384","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Caspase-3-Like Protease Activity-Independent Apoptosis at the Onset of Neuronal Cell Death in the Gerbil Hippocampus after Global Ischemia"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001206427168000","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Apoptosis of Murine Hepatocytes Induced by High Doses of Galactosamine."},{"@language":"ja-Kana","@value":"Apoptosis of murine hepatocytes induced"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681450481792","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Suppressive Effect of Caffeine on Hepatitis and Apoptosis Induced by Tumor Necrosis Factor-.ALPHA., but Not by the Anti-Fas Antibody, in Mice."},{"@value":"Suppressive Effect of Caffeine on Hepatitis and Apoptosis Induced by Tumor Necrosis Factor-α, but Not by the Anti-Fas Antibody, in Mice"},{"@language":"ja-Kana","@value":"Suppressive Effect of Caffeine on Hepatitis and Apoptosis Induced by Tumor Necrosis Factor アルファ but Not by the Anti Fas Antibody in 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