Enhanced secretion of ApoB by transfected HepG2 cells overexpressing fibrinogen.
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.
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Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67 Street, New York, New York 10021, USA.
Redman
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D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction; D000418:Albumins / Q000378:metabolism; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010743:Phospholipids / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D013261:Sterols / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000032:analysis; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D000418:Albumins; D001055:Apolipoproteins B; D015853:Cysteine Proteinase Inhibitors; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D007976:Leupeptins; D010743:Phospholipids; D012333:RNA, Messenger; D013261:Sterols; D014280:Triglycerides; D005340:Fibrinogen; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde