HBx-Induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-κB-dependent pathways

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dc.contributor.authorJ Y Kim-
dc.contributor.authorE H Song-
dc.contributor.authorH J Lee-
dc.contributor.authorY K Oh-
dc.contributor.authorK H Choi-
dc.contributor.authorDae Yeul Yu-
dc.contributor.authorS I Park-
dc.contributor.authorJ K Seong-
dc.contributor.authorW H Kim-
dc.date.accessioned2017-04-19T09:18:20Z-
dc.date.available2017-04-19T09:18:20Z-
dc.date.issued2010-
dc.identifier.issn00222836-
dc.identifier.uri10.1016/j.jmb.2010.02.016ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9483-
dc.description.abstractHepatitis B virus X (HBx) protein is an important regulator of hepatic steatosis observed in patients with hepatitis B virus; however, its underlying molecular mechanism remains unclear. TNF receptor 1 (TNFR1) is an essential pathway for the HBx-mediated nuclear factor κB (NF-κB) activation involved in hepatic liver injury. Here, we show that HBx-mediated steatosis and apoptosis are regulated by TNFR1- and NF-κB-dependent pathways. HBx-mediated tumor necrosis factor α (TNF-α) production and NF-κB activation were completely diminished in anti-TNF-α-treated cells and TNF-α-/- or TNFR1-/- mice. HBx and TNFR1, which are potentiated by TNF-α, are physically associated and colocalize in the plasma membrane. Similarly, TNFR1 depletion inhibits lipid droplets, and lipogenic genes such as sterol regulatory element binding protein (SREBP) 1 and peroxisome proliferator-activated receptor (PPAR) γ increased in HBx-Tg mice and HepG2-GFPHBx stable cells. Furthermore, lipid accumulation and expression of SREBP1c and PPARγ are significantly increased in AdHBx-GFP-injected (intravenous) wild-type mice, but not in TNFR1-/- mice. HBx-enhanced transcriptional activities of SREBP1 and PPARγ are significantly attenuated by the NF-κB inhibitor Bay 11-7082, as well as by TNFR1 depletion. Also, AdHBx-GFP potentiates TNF-α-induced apoptosis, which is completely inhibited in TNFR1-depleted cells. Our results suggest that HBx-induced NF-κB activation was mediated by direct interaction with TNFR1 and thereby induced TNF-α production. HBx-induced NF-κB activation is also associated with the induction of hepatic steatosis and apoptosis, which is determined by a TNFR1-dependent pathway.-
dc.publisherElsevier-
dc.titleHBx-Induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-κB-dependent pathways-
dc.title.alternativeHBx-Induced hepatic steatosis and apoptosis are regulated by TNFR1- and NF-κB-dependent pathways-
dc.typeArticle-
dc.citation.titleJournal of Molecular Biology-
dc.citation.number4-
dc.citation.endPage931-
dc.citation.startPage917-
dc.citation.volume397-
dc.contributor.alternativeName김지연-
dc.contributor.alternativeName송은현-
dc.contributor.alternativeName이현정-
dc.contributor.alternativeName오여경-
dc.contributor.alternativeName최경희-
dc.contributor.alternativeName유대열-
dc.contributor.alternativeName박상익-
dc.contributor.alternativeName성제경-
dc.contributor.alternativeName김원호-
dc.identifier.bibliographicCitationJournal of Molecular Biology, vol. 397, no. 4, pp. 917-931-
dc.identifier.doi10.1016/j.jmb.2010.02.016-
dc.subject.keywordApoptosis-
dc.subject.keywordHBx-
dc.subject.keywordNF-κB-
dc.subject.keywordSteatosis-
dc.subject.keywordTNFR1-
dc.subject.localApoptosis-
dc.subject.localHBx-
dc.subject.localNF-κB-
dc.subject.localNF-kB-
dc.subject.localSteatosis-
dc.subject.localTNFR1-
dc.description.journalClassY-
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