Abstract
HepG2 cells stably transfected with cDNA-encoding single fibrinogen chains overexpress fibrinogen and have increased (4-fold) secretion of apolipoprotein B. Overexpression of fibrinogen does not affect the secretion of three representative acute-phase proteins but causes a small increase in albumin secretion. Enhanced apolipoprotein B secretion is due to less intracellular degradation and not to increased expression. The increased secretion of apolipoprotein B is independent of the acute-phase response, since stimulation of fibrinogen gene expression by interleukin 6 did not affect secretion. HepG2 cells overexpressing fibrinogen chains had increased 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels, enhanced cholesterol production but normal levels of triglyceride and phospholipid synthesis and of sterol response binding proteins. These results, that associate overexpression of fibrinogen with enhance apolipoprotein B secretion, may be significant since epidemiological studies indicate that elevated levels of fibrinogen and lipids are independent risk factors in coronary artery disease.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acute-Phase Proteins / metabolism
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Acute-Phase Reaction
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Albumins / metabolism
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Apolipoproteins B / biosynthesis
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Apolipoproteins B / genetics
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Apolipoproteins B / metabolism*
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Cholesterol / biosynthesis
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Cysteine Proteinase Inhibitors / pharmacology
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DNA, Complementary / genetics
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DNA-Binding Proteins / analysis
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Fibrinogen / biosynthesis
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Fibrinogen / genetics
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Fibrinogen / metabolism*
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Humans
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Hydroxymethylglutaryl CoA Reductases / genetics
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Interleukin-6 / pharmacology
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Leupeptins / pharmacology
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Liver / drug effects
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Liver / metabolism*
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Liver / pathology
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Phospholipids / analysis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Response Elements / genetics
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Sterols / metabolism
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Transfection
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Triglycerides / analysis
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Tumor Cells, Cultured
Substances
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Acute-Phase Proteins
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Albumins
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Apolipoproteins B
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Cysteine Proteinase Inhibitors
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DNA, Complementary
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DNA-Binding Proteins
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Interleukin-6
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Leupeptins
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Phospholipids
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RNA, Messenger
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Sterols
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Triglycerides
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Fibrinogen
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Cholesterol
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Hydroxymethylglutaryl CoA Reductases
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde