| pubmed-article:18666252 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C0521447 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C0268483 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C0038952 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C2936905 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C1527148 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:18666252 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:18666252 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:18666252 | pubmed:dateCreated | 2008-8-5 | lld:pubmed |
| pubmed-article:18666252 | pubmed:abstractText | In tyrosinemia type 1 (HT1), accumulation of toxic metabolites results in oxidative stress and DNA damage, leading to a high incidence of hepatocellular carcinomas. Nuclear factor erythroid-2 related factor 2 (Nrf2) is a key transcription factor important for cellular protection against oxidative stress and chemical induced liver damage. To specifically address the role of Nrf2 in HT1, fumarylacetoacetate hydrolase (Fah)/Nrf2(-/-) mice were generated. In acute HT1, loss of Nrf2 elicited a strong inflammatory response and dramatically increased the mortality of mice. Following low grade injury, Fah/Nrf2(-/-) mice develop a more severe hepatitis and liver fibrosis. The glutathione and cellular detoxification system was significantly impaired in Fah/Nrf2(-/-) mice, resulting in increased oxidative stress and DNA damage. Consequently, tumor development was significantly accelerated by loss of Nrf2. Potent pharmacological inducers of Nrf2 such as the triterpenoid analogs 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole have been developed as cancer chemoprevention agents. Pretreatment with 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole dramatically protected Fah(-/-) mice against fumarylacetoacetate (Faa)-induced toxicity. Our data establish a central role for Nrf2 in the protection against Faa-induced liver injury; the Nrf2 regulated cellular defense not only prevents acute Faa-induced liver failure but also delays hepatocarcinogenesis in HT1. | lld:pubmed |
| pubmed-article:18666252 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18666252 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18666252 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18666252 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:18666252 | pubmed:issn | 1527-3350 | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:YamamotoMasay... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:MannsMichael... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:VogelArndtA | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:FinegoldMilto... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:SpornMichaelM | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:GrompeMarkusM | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:GeffersRobert... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:LamléJuttaJ | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:MarhenkeSilke... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:Buitrago-Moli... | lld:pubmed |
| pubmed-article:18666252 | pubmed:author | pubmed-author:CañónJosé... | lld:pubmed |
| pubmed-article:18666252 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18666252 | pubmed:volume | 48 | lld:pubmed |
| pubmed-article:18666252 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18666252 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18666252 | pubmed:pagination | 487-96 | lld:pubmed |
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| pubmed-article:18666252 | pubmed:meshHeading | pubmed-meshheading:18666252... | lld:pubmed |
| pubmed-article:18666252 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18666252 | pubmed:articleTitle | Activation of nuclear factor E2-related factor 2 in hereditary tyrosinemia type 1 and its role in survival and tumor development. | lld:pubmed |
| pubmed-article:18666252 | pubmed:affiliation | Department of Hepatology, Medical School Hannover, Hannover, Germany. | lld:pubmed |
| pubmed-article:18666252 | pubmed:publicationType | Journal Article | lld:pubmed |
| entrez-gene:18024 | entrezgene:pubmed | pubmed-article:18666252 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:18666252 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:18666252 | lld:pubmed |
