Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D.
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.
LaDuca
F M
FM
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Tinsley
L A
LA
Dang
C V
CV
Bell
W R
WR
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
D005338:Fibrin Fibrinogen Degradation Products; D013462:Sulfur Radioisotopes; C015214:fibrinogen D fragment; D005340:Fibrinogen; D008715:Methionine; D006854:Hydrocortisone