Polyamine depletion results in impairment of polyribosome formation and protein synthesis before onset of DNA synthesis in mitogen-activated human lymphocytes.
Lymphocytes, exposed to mitogens in culture, show enhanced protein and RNA synthesis before the onset of DNA synthesis. Inhibition by DL-alpha-difluoromethylornithine of polyamine synthesis in phytohaemagglutinin-activated human lymphocytes resulted in a suppression of protein synthesis, which was evident before the initiation of DNA synthesis. The mitogen-induced increase in the incorporation of [3H]thymidine into DNA was subsequently inhibited in parallel with the activity of thymidine kinase in the polyamine-depleted cells. Ultraviolet absorbance measurement of the ribosomes after sucrose gradient centrifugation revealed a suppression of polyribosome formation that coincided with the decrease in the rate of protein synthesis. The disturbance in the polysomal profiles did not appear to be due to a shortage of mRNA, since the synthesis of poly(A)-rich mRNA was reduced less than that of rRNA after inhibiting polyamine synthesis. Entry of both the pre-existing and newly synthesized ribosomal subunits into polysomal structures was found to be impaired. These results thus suggest an important role for polyamines in the initiation step of protein synthesis.
D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D000518:Eflornithine; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D011073:Polyamines / Q000172:deficiency*; D011132:Polyribosomes / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D012335:RNA, Ribosomal / Q000096:biosynthesis
D008934:Mitogens; D011073:Polyamines; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D004247:DNA; D009952:Ornithine; D000518:Eflornithine