EFFECTS OF ACTINOMYCIN D ON BIOSYNTHESIS OF PLASMA LIPOPROTEINS

Intraperitoneal administration of actinomycin D, particularly when supplementary injections were given, severely inhibited orotic acid incorporation into the trichloroacetic acid precipitate of rat liver for several hours and resulted in a decrease in the principal low density lipoprotein component of rat serum, which was still apparent after 21 hr. At the same time the concentration of high density lipoproteins was found to increase slightly. The biosynthesis of lipoproteins was measured by following L- [3H]lysine incorporation into the lipoprotein protein moieties, both in vivo and in the isolated perfused liver. In both cases actinomycin D pretreatment caused a greater inhibition of low density lipoprotein synthesis than that of high density lipoprotein. Specific activity determinations on a number of protein fractions isolated from the perfusate and from the liver after a liver perfusion demonstrated that the decreases in synthesis observed after actinomycin D treatment vary considerably for different proteins, indicating a general heterogeneity of hepatic template stability. © 1968, American Chemical Society. All rights reserved.