Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D
- Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)
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.
- OSTI ID:
- 5102408
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:22; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
FIBRINOGEN
BIOSYNTHESIS
HYDROCORTISONE
BIOCHEMICAL REACTION KINETICS
LIVER CELLS
METHIONINE
RATS
SULFUR 35
TRACER TECHNIQUES
ADRENAL HORMONES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD COAGULATION FACTORS
CARBOXYLIC ACIDS
COAGULANTS
CORTICOSTEROIDS
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
GLOBULINS
GLUCOCORTICOIDS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PREGNANES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEROIDS
SULFUR ISOTOPES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques