{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:42:12Z","timestamp":1790775732571,"version":"4.1.0"},"reference-count":7,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2007,5,29]],"date-time":"2007-05-29T00:00:00Z","timestamp":1180396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Death receptor\u2010mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia\/reperfusion injury, fulminant hepatic failure, cholestatic liver injury, and cancer. Our aim was to clarify the protective pathway in death receptor\u2010mediated hepatocyte apoptosis and the significance of apoptosis in liver injury. <jats:italic>In vitro<\/jats:italic>: AdI\u03baBsr plus tumor necrosis factor (TNF)\u2010\u03b1\/Jo2 rapidly induced apoptosis in mouse hepatocyte, whereas TNF\u2010\u03b1\/Jo2 alone produced little cytotoxicity. The combination of the mitochondrial permeability transition (MPT) inhibitors, cyclosporine A and trifluoperazine, protected AdI\u03baBsr\u2010infected hepatocytes from TNF\u2010\u03b1\u2010 but not Fas\u2010mediated apoptosis. The TNF\u2010\u03b1 and Jo2 induced iNOS through NF\u2010\u03baB. Nitric oxide donor (S\u2010nitroso\u2010N\u2010acetylpenicillamine) inhibited Bid cleavage, the MPT, and caspase activation and reduced TNF\u2010\u03b1\u2010 and Fas\u2010mediated cell killing. Inhibition of PI3K by LY294002 and a dominant\u2010negative Akt, which attenuated NF\u2010\u03baB activation by TNF\u2010\u03b1 or Jo2, sensitized hepatocytes to TNF\u2010<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/JGH_4645_mu1.gif\" xlink:title=\"inline image\"\/> or Jo2. <jats:italic>In vivo<\/jats:italic>: apoptosis as well as necrosis may play an important role in hepatic ischemia\/reperfusion injury. Adenoviral gene transfer of myrAkt could inhibit apoptotic cell death and subsequent hepatic ischemia\/reperfusion injury in the rat, through Bad not NF\u2010\u03baB. Bile acids cause liver injury during cholestasis by inducing hepatocyte apoptosis. Hepatocyte apoptosis has a major role in hepatic injury by bile duct ligation. At least, early hepatic injury by bile duct ligation involved Fas\u2010mediated and Bcl\u2010xL insensitive apoptotic pathway. In conclusion, the role of apoptosis in various liver diseases may suggest possible treatments.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2006.04645.x","type":"journal-article","created":{"date-parts":[[2007,5,30]],"date-time":"2007-05-30T02:08:14Z","timestamp":1180490894000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Tumor necrosis factor signaling in hepatocyte apoptosis"],"prefix":"10.1111","volume":"22","author":[{"given":"Etsuro","family":"Hatano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.16.11814"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.23239"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.281.6.G1357"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2004.04.016"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.043034"},{"key":"e_1_2_6_7_2","first-page":"1301","article-title":"Blocking of PI3K\/Akt pathway enhances apoptosis induced by SN\u201038, an active form of CPT\u201011, in human hepatoma cells","volume":"26","author":"Koizumi N","year":"2005","journal-title":"Int. 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Oncol."},{"key":"e_1_2_6_8_2","first-page":"300A","article-title":"Overexpression of truncated FADD, but not Bcl\u2010xL, attenuates liver injury in bile duct\u2010ligated mice; The effect of anti\u2010apoptotic therapy on cholestatic liver injury","volume":"36","author":"Nitta T","year":"2002","journal-title":"Hepatology"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1440-1746.2006.04645.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1440-1746.2006.04645.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T06:39:42Z","timestamp":1695796782000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1440-1746.2006.04645.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,29]]},"references-count":7,"journal-issue":{"issue":"s1","published-print":{"date-parts":[[2007,6]]}},"alternative-id":["10.1111\/j.1440-1746.2006.04645.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1440-1746.2006.04645.x","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,29]]},"assertion":[{"value":"2007-05-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}