Bezafibrate down-regulates fibrinogen biosynthesis in human hepatoma HepG2 cells.
BACKGROUND
Bezafibrate reportedly lowers serum lipids and plasma fibrinogen in humans and rats, but the mechanism of this process has still to be clarified. We have addressed this problem by investigating the effects of bezafibrate on fibrinogen in the human hepatoma HepG2 cell line.


METHODS
In cells cultured with and without bezafibrate, intra- and extracellular fibrinogen was quantified using an enzyme-linked immunosorbent assay (ELISA), and changes in the biosynthesis and secretion of bezafibrate were monitored by [35S]-methionine labelling. In addition, expression of the corresponding mRNA was investigated by Northern blotting. As fibrinogen is an acute-phase protein, HepG2 cells exposed to interleukin 6 were also analysed.


RESULTS
Bezafibrate decreased fibrinogen biosynthesis by about 25%, regardless of whether or not the cultures were also exposed to interleukin 6. mRNA was reduced in proportion to the concentration of interleukin 6 to which the cells were exposed, but intracellular transport and release of the protein were not affected.


CONCLUSIONS
Apparently, bezafibrate interferes with the biosynthesis of fibrinogen at the pretranslational level but does not affect the export of the protein.
Binsack
R
R
Boehringer Mannheim, Germany.
Stegmeier
K
K
Dörge
L
L
Völkl
A
A
D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000502:physiology; D005340:Fibrinogen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism; D011233:Precipitin Tests; D012334:RNA, Neoplasm / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D037102:Lectins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D005340:Fibrinogen; D001629:Bezafibrate