Search

The effects of malotilate (diisoporpyl 1,3-dithiol-2-ylidenemalonate) on the synthesis and movement of RNA in rat liver were studied in order to elucidate the mechanism of protein synthesis induced by this drug. Incorporation of 3H-cytidine into various RNAs was followed to determine the rates of their synthesis. Oral administration of malotilate to rats enhanced the total RNA synthesis, which reached to maximum level 3 hr after administration. At that time, the increases in the incorporation of radioactivities into the total RNA and the nucleotide pool were closely related to the dosages. Malotilate significantly increased the polyribosomal and t-RNA synthesis as well as nuclear RNA, but not the movement of RNA from the nuclei to the cytosol. It is not likely that malotilate activates specific genes in chromatin because only about 0.1 nmole of malotilate and its metabolites per mg DNA was found in chromatin. From these results, a possible mechanism of protein synthesis induced by malotilate can be proposed as follows: malotilate primarily affects the post-transcription process, promoting the RNA synthesis in the nuclear fraction without any changes of DNA synthesis, and these consequent increases of the polyribosomal RNA and t-RNA synthesis result in the enhancement of protein synthesis.