Source:http://linkedlifedata.com/resource/pubmed/id/18393316
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2008-5-1
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pubmed:abstractText |
Cytochrome P450 2E1 (CYP2E1) is suggested to play a role in alcoholic liver disease, which includes alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. In this study, we investigated whether CYP2E1 plays a role in experimental alcoholic fatty liver in an oral ethanol-feeding model. After 4 weeks of ethanol feeding, macrovesicular fat accumulation and accumulation of triglyceride in liver were observed in wild-type mice but not in CYP2E1-knockout mice. In contrast, free fatty acids (FFAs) were increased in CYP2E1-knockout mice but not in wild-type mice. CYP2E1 was induced by ethanol in wild-type mice, and oxidative stress induced by ethanol was higher in wild-type mice than in CYP2E1-knockout mice. Peroxisome proliferator-activated receptor alpha (PPARalpha), a regulator of fatty acid oxidation, was up-regulated in CYP2E1-knockout mice fed ethanol but not in wild-type mice. A PPARalpha target gene, acyl CoA oxidase, was decreased by ethanol in wild-type but not in CYP2E1-knockout mice. Chlormethiazole, an inhibitor of CYP2E1, lowered macrovesicular fat accumulation, inhibited oxidative stress, and up-regulated PPARalpha protein level in wild-type mice fed ethanol. The introduction of CYP2E1 to CYP2E1-knockout mice via an adenovirus restored macrovesicular fat accumulation. These results indicate that CYP2E1 contributes to experimental alcoholic fatty liver in this model and suggest that CYP2E1-derived oxidative stress may inhibit oxidation of fatty acids by preventing up-regulation of PPARalpha by ethanol, resulting in fatty liver.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alanine Transaminase,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP2E1,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Nonesterified,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Thiobarbituric Acid Reactive...,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1527-3350
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1483-94
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pubmed:meshHeading |
pubmed-meshheading:18393316-Alanine Transaminase,
pubmed-meshheading:18393316-Animals,
pubmed-meshheading:18393316-Cytochrome P-450 CYP2E1,
pubmed-meshheading:18393316-Disease Models, Animal,
pubmed-meshheading:18393316-Ethanol,
pubmed-meshheading:18393316-Fatty Acids, Nonesterified,
pubmed-meshheading:18393316-Fatty Liver, Alcoholic,
pubmed-meshheading:18393316-Female,
pubmed-meshheading:18393316-Immunohistochemistry,
pubmed-meshheading:18393316-Liver,
pubmed-meshheading:18393316-Mice,
pubmed-meshheading:18393316-Mice, Knockout,
pubmed-meshheading:18393316-PPAR alpha,
pubmed-meshheading:18393316-Thiobarbituric Acid Reactive Substances,
pubmed-meshheading:18393316-Triglycerides,
pubmed-meshheading:18393316-Tumor Necrosis Factor-alpha
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pubmed:year |
2008
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pubmed:articleTitle |
Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice.
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pubmed:affiliation |
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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