title: Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D.
abstract: The direct stimulation of fibrinogen biosynthesis by fibrinogen degradation produces (FDPs) was studied in rat hepatocyte cultures. Pure rat FDP fragment D (FDP-D) (Mr 90,000) and FDP fragment E (FDP-E) (Mr 40,000) and mixtures of the two (FDP-DE) were added to rat hepatocytes cultured in serum-free hormonally defined medium. Hydrocortisone (20 microM) significantly increased synthesis of fibrinogen, as determined by incorporation of [35S]methionine. FDP-D and FDP-E did not increase fibrinogen synthesis in the presence of hydrocortisone. However, hepatocytes cultured without hydrocortisone displayed increased fibrinogen synthesis (2.0- to 2.8-fold) with FDP-D (2.6-6.7 microM) but not with FDP-E (5.7 microM). At these FDP concentrations the synthesis of albumin, haptoglobin, and transferrin was not increased. FDP-D-induced fibrinogen synthesis was inhibited (greater than 90%) by actinomycin D and cycloheximide, indicating that the increase in [35S]methionine incorporation was from de novo protein synthesis. The role of FDP-D was further substantiated by showing that FDP-D, but not FDP-E, bound to the hepatocytes. These data indicate that FDP-D, but not FDP-E, directly and specifically stimulates fibrinogen synthesis in rat hepatocytes; this stimulation does not require any additional serum or protein cofactors.
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors: F M
authors: FM
authors: LaDuca
authors: L A
authors: LA
authors: Tinsley
authors: C V
authors: CV
authors: Dang
authors: W R
authors: WR
authors: Bell
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism / Q000494:pharmacology*; D005340:Fibrinogen / Q000096:biosynthesis*; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013462:Sulfur Radioisotopes
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D013462:Sulfur Radioisotopes; C015214:fibrinogen D fragment; D005340:Fibrinogen; D008715:Methionine; D006854:Hydrocortisone