benzyloxycarbonylleucyl-leucyl-leucine-aldehyde and Acute-Phase-Reaction

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.

Topics: Acute-Phase Proteins; Acute-Phase Reaction; Albumins; Apolipoproteins B; Cholesterol; Cysteine Proteinase Inhibitors; DNA-Binding Proteins; DNA, Complementary; Fibrinogen; Humans; Hydroxymethylglutaryl CoA Reductases; Interleukin-6; Leupeptins; Liver; Phospholipids; Response Elements; RNA, Messenger; Sterols; Transfection; Triglycerides; Tumor Cells, Cultured