| Mitochondrial dysfunction in cholestatic liver diseases. | |
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MedLine Citation:
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PMID: 22202034 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Cholestatic liver diseases are characterized by blockade of bile flow from the liver to the intestine, and accumulation of hydrophobic bile acids in the liver and plasma. As a consequence an inflammatory response evolves associated with increased apoptosis, oxidative stress, and eventually fibrosis. Cholestasis is associated with profound metabolic changes, alterations in the mitochondrial function, decreased fatty acid oxidation, and increased glycolisis. Mitochondria play a central role in the development of this liver disease because they mediate death receptor signaling - triggered by inflammatory cytokines or bile acids - and contribute to oxidative damage, metabolic disorder, and onset of fibrosis. During the pathogenesis of biliary cirrhosis mitochondria's need for renewal is hampered by a blunted mitochondrial biogenesis. Lack of stimulation of mitochondrial renewal helps to explain mitochondrial impairment in long-term cholestasis. The marked depletion of mitochondrial DNA and occurrence of mitochondrial DNA deletions are probably relevant contributors to the progression of this severe disease. All these findings certainly support the consideration of long-term cholestasis as a secondary mitochondrial hepatopathy. |
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Authors:
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Alessandro Arduini; Gaetano Serviddio; Ana M Tormos; Maria Monsalve; Juan Sastre |
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Publication Detail:
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Type: Journal Article Date: 2012-01-01 |
Journal Detail:
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Title: Frontiers in bioscience (Elite edition) Volume: 4 ISSN: 1945-0508 ISO Abbreviation: Front Biosci (Elite Ed) Publication Date: 2012 |
Date Detail:
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Created Date: 2011-12-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101485240 Medline TA: Front Biosci (Elite Ed) Country: United States |
Other Details:
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Languages: eng Pagination: 2233-52 Citation Subset: IM |
Affiliation:
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Department of Physiology, School of Pharmacy, University of Valencia, Valencia, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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