Source:http://linkedlifedata.com/resource/pubmed/id/20457138
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2010-7-8
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pubmed:abstractText |
Oxidative stress is known to be a common feature of cholestatic syndrome. Lipopolysaccharide (LPS) induces cholestasis, causing multidrug resistance-associated protein 2 (Mrp2) downregulation in two different ways: early retrieval from the canalicular membrane and the latter event of reduced mRNA expression. However, the triggering factor for LPS-induced cholestasis is not fully understood. In this study, we examined the effect of dimerumic acid (DMA), an antioxidant and traditional Chinese medicine, on endotoxin-induced Mrp2 downregulation in rat liver. At 3h following LPS injection (4mg/kg body weight), canalicular Mrp2 localization was disrupted without changing the expression of Mrp2 protein or the integrity of tight junctions in the liver. Pretreatment with DMA (12mg/kg body weight) counteracted LPS-induced subcellular distribution, and decreased the bile flow rate and biliary glutathione (GSH) excretion. At 12h following LPS injection, Mrp2 protein and mRNA expression were significantly decreased by 58% and 7%, respectively. In contrast, pretreatment with DMA did not have any effect on the decreased Mrp2 expression and biliary excretion of GSH induced by LPS exposure. Taken together, our data clearly indicate that LPS-induced short-term rapid retrieval of Mrp2 from the canalicular surface resulted from LPS-induced oxidative stress, while the long-term transcriptional regulation of Mrp2 expression did not depend on the intracellular redox status.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/dimerum acid,
http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1873-2968
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pubmed:author | |
pubmed:copyrightInfo |
2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
533-9
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pubmed:meshHeading |
pubmed-meshheading:20457138-Animals,
pubmed-meshheading:20457138-Down-Regulation,
pubmed-meshheading:20457138-Gene Expression Regulation,
pubmed-meshheading:20457138-Lipopolysaccharides,
pubmed-meshheading:20457138-Liver,
pubmed-meshheading:20457138-Male,
pubmed-meshheading:20457138-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:20457138-Piperazines,
pubmed-meshheading:20457138-Rats,
pubmed-meshheading:20457138-Rats, Wistar
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pubmed:year |
2010
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pubmed:articleTitle |
The effect of dimerumic acid on LPS-induced downregulation of Mrp2 in the rat.
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pubmed:affiliation |
Chiba University, Inohana, Chuo-ku, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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