| http://purl.uniprot.org/citations/15633127 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15633127 | http://www.w3.org/2000/01/rdf-schema#comment | "Background & aimsAlcohol consumption exacerbates liver injury in chronic hepatitis C, and enhanced mitochondrial oxidative stress is one possible mechanism. The aim of this study was to determine whether hepatitis C virus core protein and alcohol-inducible cytochrome P450 2E1 contribute to reactive oxygen species production and cytotoxicity in human hepatoma cells.MethodsHuh-7 cells expressing core protein, cytochrome P450 2E1, or both were exposed to 0.1 mmol/L tertiary butyl hydroperoxide, tumor necrosis factor alpha, and/or 25 mmol/L ethanol. Cytotoxicity, reactive oxygen species production, glutathione content, and mitochondrial membrane potential were measured.ResultsExpression of core/cytochrome P450 2E1 synergistically enhanced cell death induced by either tertiary butyl hydroperoxide or tumor necrosis factor alpha. After tertiary butyl hydroperoxide treatment, total reactive oxygen species production was increased more than 3-fold compared with cells that did not express core and cytochrome P450 2E1. Mitochondrial depolarization and reduced glutathione depletion occurred as well, and cell death was prevented by inhibition of mitochondrial permeability transition or caspase activity. Confocal microscopy showed that the mitochondria themselves were the origin of the reactive oxygen species. In the absence of core/cytochrome P450 2E1 expression, mitochondrial changes and cell death did not occur. Ethanol treatment further decreased mitochondrial reduced glutathione content and exacerbated mitochondrial reactive oxygen species production, depolarization, and cell death. All these effects were prevented by the antioxidant N -acetylcysteine.ConclusionsMitochondrial reactive oxygen species production is induced by hepatitis C virus core and cytochrome P450 2E1, resulting in a reduction of mitochondrial antioxidant capacity and sensitivity to oxidants and tumor necrosis factor alpha. Alcohol further depletes mitochondrial reduced glutathione, which exacerbates depolarization and cell death. Sensitization of mitochondria to oxidative insults is thus a potential mechanism for alcohol-related exacerbation of liver injury in chronic hepatitis C."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.org/dc/terms/identifier | "doi:10.1053/j.gastro.2004.10.045"xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Li K."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Singh A.K."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Weinman S.A."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Qian T."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Beard M.R."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Showalter L.A."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Otani K."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/author | "Korenaga M."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/name | "Gastroenterology"xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/pages | "96-107"xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/title | "Hepatitis C virus core protein, cytochrome P450 2E1, and alcohol produce combined mitochondrial injury and cytotoxicity in hepatoma cells."xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://purl.uniprot.org/core/volume | "128"xsd:string |
| http://purl.uniprot.org/citations/15633127 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15633127 |
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| http://purl.uniprot.org/uniprot/#_Q16868-mappedCitation-15633127 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15633127 |