Source:http://linkedlifedata.com/resource/pubmed/id/10580514
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1999-12-16
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pubmed:abstractText |
Chronic alcohol exposure leads to the appearance of carbohydrate-deficient transferrin (CDT), a N-glycosylated protein and sialic acid-deficient apolipoprotein E (apoE), an O-glycosylated protein. We show that chronic ethanol treatment destabilizes sialyltransferase (ST) mRNA resulting in a concomitant decreased steady-state level of ST mRNA. As a result, alcohol markedly decreases the hepatic synthetic rate of ST. This leads to impaired sialylation of transferrin and apoE. Consequently, apoE content in plasma high-density lipoproteins (HDL) is decreased. ApoE plays a significant role in the delivery of HDL cholesterol to the liver via apo B/E receptor, a process called reverse cholesterol transport (RCT). Desialylation of apoE results in its decreased association with HDL. Thus, the dissociation constant of HDL for binding to sialo-apoE is 90 +/- 35 nM, whereas that for desialo-apoE is 1010 +/- 250 nM. More importantly, the uptake of labeled cholesterol by human HepG2 cells is decreased by 30-40% from reconstituted HDL particles (rHDL)-containing desialo-apoE compared to rHDL with sialo-apoE. We conclude that chronic alcohol exposure down-regulates the expression of sialyltransferase genes resulting in impaired sialylation of apoE. This leads to its decreased binding to plasma HDL and thereby, impairs the RCT function of HDL.
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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/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Depressants,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, HDL,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sialyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/beta-D-galactoside alpha...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0741-8329
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
239-47
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10580514-Animals,
pubmed-meshheading:10580514-Apolipoproteins E,
pubmed-meshheading:10580514-Central Nervous System Depressants,
pubmed-meshheading:10580514-Cholesterol, HDL,
pubmed-meshheading:10580514-Cholesterol, VLDL,
pubmed-meshheading:10580514-Ethanol,
pubmed-meshheading:10580514-Glycosylation,
pubmed-meshheading:10580514-Liver,
pubmed-meshheading:10580514-RNA, Messenger,
pubmed-meshheading:10580514-Rats,
pubmed-meshheading:10580514-Rats, Inbred WF,
pubmed-meshheading:10580514-Sialyltransferases
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pubmed:year |
1999
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pubmed:articleTitle |
Alcohol and molecular regulation of protein glycosylation and function.
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pubmed:affiliation |
Lipid Research Laboratory, DVA Medical Center, and Department of Medicine, The George Washington University, Washington, DC 20422, USA. rlax@erols.com
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pubmed:publicationType |
Journal Article
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