The effects of warfarin on HepG2 cells suggest that prothrombin and factor X interact differently with the vitamin K-dependent carboxylase in the secretory pathway.
HepG2 cells have been shown to respond to warfarin by 1) enhanced vitamin K-dependent carboxylase activity; 2) enhanced intracellular concentration of the factor X clotting factor precursor and 3) enhanced vitamin K-dependent 14C-labelling of a 74 kDa microsomal protein which has been identified as the factor X precursor. There was no difference in any of these measured parameters whether the cells had been treated for 4 or 24 hours with warfarin. In contrast to the intracellular factor X concentration, the intracellular prothrombin precursor concentration was not affected by the drug which suggests there is a difference in the mechanism of processing of these two clotting factors by HepG2 cells. The data are consistent with the view that warfarin maintains its effect on the vitamin K-dependent carboxylation system in HepG2 cells for 24 hours and support the hypothesis that clotting factor X and prothrombin precursors interact differently with the vitamin K-dependent carboxylase.
Wallin
R
R
Department of Medicine, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, North Carolina.
D019735:Carbon-Carbon Ligases; D005170:Factor X / Q000378:metabolism*; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014859:Warfarin / Q000494:pharmacology*
D014859:Warfarin; D011516:Prothrombin; D005170:Factor X; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase