Prothrombin Synthesis and Degradation in Rat Hepatoma (H-35) Cells: Effects of Warfarin

Vitamin K is a substrate for the enzyme catalyzing the carboxylation of specific glutamyl residues to y-carboxyglutamy1 residues in hepatic precursors of a limited number of plasma proteins, including prothrombin. The y-carboxylation of these proteins can be blocked by the anticoagulant warfarin; and in the bovine and human, warfarin treatment results in the secretion of under-y-carboxylated forms of prothrombin into plasma. In the rat, this response is not seen, but plasma prothrombin concentrations are drastically decreased. This response has now been studied in rat hepatoma (H-35) cells in which prothrombin secretion is decreased 90% by incubation in the presence of warfarin. Neither prothrombin mRNA levels nor the apparent rate of prothrombin message translation were decreased when cells were cultured in the presence of warfarin rather than