{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:39:03Z","timestamp":1790987943345,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6028,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Fundaci\u00f3n para el Estudio de las Hepatitis Virales, Madrid, Spain. M.J.A. is a research fellow of the Fundaci\u00f3n Conchita R\u00e1bago, Madrid, Spain"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The capability of hepatitis B virus (HBV) to increase the transcription of the human hepatic inducible nitric oxide synthase (iNOS) by transactivating its promoter has been studied. We have observed by reverse\u2013transcription polymerase chain reaction (RT\u2013PCR) that although the mRNA for the iNOS was almost undetectable in the human hepatoblastoma cell line, HepG2, it was constitutively expressed in the 2.2.15 cell line (a derivative of the HepG2 that produces complete HBV particles). Transfection of HepG2 and 2.2.15 cells with the p1iNOS\u2013CAT plasmid (containing a 1.1\u2013kb fragment of the iNOS promoter) resulted in an increase in chloramphenicol acetyl transferase (CAT) activity in 2.2.15 cells. Similar results were observed when HepG2 and Chang liver cell lines were cotransfected with the p1iNOS\u2013CAT plasmid and the complete HBV genome. It was shown that pX was responsible for the transactivation by cotransfection of HepG2 cells with the p1iNOS\u2013CAT and plasmids expressing the HBV\u2013encoded pX protein, core antigen, and e antigen. Cotransfection of HepG2 cells with the pX expression plasmids and a series of deletion mutants of the 1.1\u2013kb iNOS promoter fragments established that transactivation by pX depends on the presence of at least one nuclear factor\u2013\u03baB (NF\u2013\u03baB) binding site. This was further confirmed by cotransfecting cells with a plasmid expressing the NF\u2013\u03baB inhibitor, I\u03baB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510290337","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:25:38Z","timestamp":1090999538000},"page":"915-923","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Hepatitis B Virus X Protein Transactivates the Inducible Nitric Oxide Synthase Promoter"],"prefix":"10.1097","volume":"29","author":[{"given":"Maria Jos\u00e9","family":"Amaro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Bartolom\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Carre\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.510290337-BIB1|cit1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1146\/annurev.bi.56.070187.003251","article-title":"The molecular biology of the hepatitis B virus","volume":"56","author":"Ganem","year":"1987","journal-title":"Annu Rev Biochem"},{"key":"10.1002\/hep.510290337-BIB2|cit2","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/hep.1840090226","article-title":"Compact organization of the hepatitis B virus genome","volume":"9","author":"Miller","year":"1989","journal-title":"Hepatology"},{"key":"10.1002\/hep.510290337-BIB3|cit3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jmv.1890360207","article-title":"Review: hepatitis B virus X-gene product: a promiscuous transcriptional activator","volume":"36","author":"Rossner","year":"1992","journal-title":"J Med Virol"},{"key":"10.1002\/hep.510290337-BIB4|cit4","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1128\/JVI.66.2.983-991.1992","article-title":"Hepatitis B virus protein activates transcription factor NF\u03baB without a requirement for protein kinase C","volume":"66","author":"Lucito","year":"1992","journal-title":"J Virol"},{"key":"10.1002\/hep.510290337-BIB5|cit5","first-page":"109","article-title":"Nitric oxide: physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada","year":"1991","journal-title":"Pharmacol Rev"},{"key":"10.1002\/hep.510290337-BIB6|cit6","doi-asserted-by":"crossref","first-page":"227","DOI":"10.7326\/0003-4819-120-3-199402010-00009","article-title":"Nitric oxide, a physiologic messenger","volume":"120","author":"Lowenstein","year":"1994","journal-title":"Ann Intern Med"},{"key":"10.1002\/hep.510290337-BIB7|cit7","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1073\/pnas.90.8.3491","article-title":"Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes","volume":"90","author":"Geller","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.510290337-BIB8|cit8","first-page":"1552","article-title":"Further characterization and comparison of inducible nitric oxide synthase in mouse, rat and human hepatocytes","volume":"21","author":"Nussler","year":"1995","journal-title":"Hepatology"},{"key":"10.1002\/hep.510290337-BIB9|cit9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1084\/jem.176.1.261","article-title":"Stimulation of nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin","volume":"176","author":"Nussler","year":"1992","journal-title":"J Exp Med"},{"key":"10.1002\/hep.510290337-BIB10|cit10","first-page":"3925","article-title":"Elevated formation of nitrate and N-nitrosodimethylamine in woodchucks (Marmota monax) associated with chronic woodchuck hepatitis virus infection","volume":"51","author":"Liu","year":"1991","journal-title":"Cancer Res"},{"key":"10.1002\/hep.510290337-BIB11|cit11","first-page":"4139","article-title":"Nitrite and nitrosamine synthesis by hepatocites isolated from normal woodchucks (Marmota Monax) and woodchucks chronically infected with woodchuck hepatitis virus","volume":"52","author":"Lui","year":"1992","journal-title":"Cancer Res"},{"key":"10.1002\/hep.510290337-BIB12|cit12","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI774","article-title":"Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation","volume":"101","author":"Majano","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.510290337-BIB13|cit13","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1006\/bbrc.1994.1522","article-title":"Promoter analysis of human inducible nitric oxide synthase gene associated with cardiovascular homeostasis","volume":"200","author":"Nunokawa","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/hep.510290337-BIB14|cit14","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1073\/pnas.84.4.1005","article-title":"Production of hepatitis B virus particles in HepG2 cells transfected with cloned hepatitis B virus DNA","volume":"84","author":"Sells","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.510290337-BIB15|cit15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/bbrc.1996.0897","article-title":"Human inducible nitric oxide synthase gene is transcriptionally regulated by nuclear factor-kB dependent mechanism","volume":"223","author":"Nunokawa","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/hep.510290337-BIB16|cit16","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1093\/clinchem\/31.6.831","article-title":"Radioimmunoassay for detecting hepatitis B core antigen in serum from patients with chronic hepatitis B infection","volume":"31","author":"Quiroga","year":"1985","journal-title":"Clin Chem"},{"key":"10.1002\/hep.510290337-BIB17|cit17","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/0006-291X(91)90379-L","article-title":"Full-length and truncated versions of the hepatitis B virus (HBV) X protein (pX) transactivate the cMYC protooncogene at the transcriptional level","volume":"176","author":"Balsano","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/hep.510290337-BIB18|cit18","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1006\/bbrc.1993.1359","article-title":"Pyrrolidine dithiocarbamate inhibits induction of nitric oxide synthase activity in rat alveolar macrophages","volume":"191","author":"Sherman","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/hep.510290337-BIB19|cit19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000149651","article-title":"Taxonomic classification of human hepatitis B virus","volume":"25","author":"Gut","year":"1986","journal-title":"Intervirology"},{"key":"10.1002\/hep.510290337-BIB20|cit20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01308334","article-title":"Hepatitis B virus, new and evolving issues","volume":"37","author":"Yoffe","year":"1992","journal-title":"Dig Dis Sci"},{"key":"10.1002\/hep.510290337-BIB21|cit21","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/carcin\/15.12.2875","article-title":"Woodchuck hepatitis virus surface antigen induces nitric oxide synthesis in hepatocytes: possible role in hepatocarcinogenesis","volume":"15","author":"Liu","year":"1994","journal-title":"Carcinogenesis"},{"key":"10.1002\/hep.510290337-BIB22|cit22","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1101\/gad.9.22.2723","article-title":"ReI\/F-\u03baB\/I\u03baB family: intimate tales of association and dissociation","volume":"9","author":"Verma","year":"1995","journal-title":"Genes Dev"},{"key":"10.1002\/hep.510290337-BIB23|cit23","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.179.3.841","article-title":"Induction of Tumor Necrosis Factor production by human hepatocytes in chronic viral hepatitis","volume":"179","author":"Gonz\u00e1lez-Amaro","year":"1994","journal-title":"J Exp Med"},{"key":"10.1002\/hep.510290337-BIB24|cit24","doi-asserted-by":"crossref","first-page":"8339","DOI":"10.1016\/S0021-9258(19)39077-5","article-title":"Protein Kinase C independent activation of nuclear factor \u03baB by tumor necrosis factor","volume":"265","author":"Meichle","year":"1990","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.510290337-BIB25|cit25","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1073\/pnas.87.4.1620","article-title":"Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide","volume":"87","author":"Beckman","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1002\/hep.510290337-BIB26|cit26","doi-asserted-by":"crossref","first-page":"26066","DOI":"10.1016\/S0021-9258(18)47160-8","article-title":"Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation","volume":"269","author":"Rubbo","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.510290337-BIB27|cit27","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1097\/00003246-199211000-00015","article-title":"Nitric oxide synthesis serves to reduce hepatic damage during acute murine endotoxemia","volume":"20","author":"Harbrecht","year":"1992","journal-title":"Crit Care Med"},{"key":"10.1002\/hep.510290337-BIB28|cit28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/cvr\/26.1.48","article-title":"Protective and pathological roles of nitric oxide in endotoxin shock","volume":"26","author":"Wright","year":"1992","journal-title":"Cardiovasc Res"},{"key":"10.1002\/hep.510290337-BIB29|cit29","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/0024-3205(92)90064-V","article-title":"Role of nitric oxide in the oxidant stress during ischemia\/reperfusion injury of the liver","volume":"50","author":"Jaeschke","year":"1992","journal-title":"Life Sci"},{"key":"10.1002\/hep.510290337-BIB30|cit30","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0016-5085(95)90075-6","article-title":"Endotoxin stimulated nitric oxide production increases injury and reduces rat liver chemiluminiscence during reperfusion","volume":"108","author":"Mittal","year":"1995","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.510290337-BIB31|cit31","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1096\/fasebj.5.7.1707021","article-title":"Nitric oxide and nitric oxide-generating compounds inhibit hepatocyte protein synthesis","volume":"5","author":"Curran","year":"1991","journal-title":"FASEB J"},{"key":"10.1002\/hep.510290337-BIB32|cit32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.iy.13.040195.000333","article-title":"Hepatitis B virus immunopathogenesis","volume":"13","author":"Chisari","year":"1995","journal-title":"Annu Rev Immunol"},{"key":"10.1002\/hep.510290337-BIB33|cit33","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1042\/bj2810419","article-title":"Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide","volume":"281","author":"Hogg","year":"1992","journal-title":"Biochem J"},{"key":"10.1002\/hep.510290337-BIB34|cit34","doi-asserted-by":"crossref","first-page":"8857","DOI":"10.1016\/S0021-9258(17)37047-3","article-title":"Negative regulation of hepatitis B virus gene expression and replication by oxidative stress","volume":"269","author":"Zheng","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.510290337-BIB35|cit35","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1093\/nar\/11.6.1747","article-title":"The complete nucleotide sequence of the cloned hepatitis B virus DNA; subtype adr and adw","volume":"19","author":"Ono","year":"1983","journal-title":"Nucleic Acids Res"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.510290337","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199903000-00041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:27:35Z","timestamp":1733052455000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199903000-00041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1999]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.510290337","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1999,3]]}}}