Chloramphenicol inhibits hormone-dependent induction of cytoplasmic mRNA coding for the mitochondrial enzyme, carbamyl phosphate synthetase, in Rana catesbeiana tadpoles.
In tadpoles injected with thyroxine (T4), synthesis of carbamyl phosphate synthetase 1 is induced so that within 7-8 days this single polypeptide represents one of the most abundant proteins in the liver. Translational assays in vitro showed that liver RNA from control animals had very low levels of translatable mRNA coding for the enzyme whereas carbamyl phosphate synthetase mRNA activity was prominent in liver from tadpoles which had been treated with T4 for just 2 days. When the primary translation product of carbamyl phosphate synthetase mRNA was immunoprecipitated from a messenger-dependent rabbit reticulocyte cell-free system programmed with total liver mRNA, it migrated on SDS-polyacrylamide gels more slowly than the in vivo form of the enzyme and otherwise demonstrated characteristics which were very similar to the precursor for carbamyl phosphate synthetase previously described in rat liver. If tadpoles were treated for 2 days with T4 plus an inhibitor of mitochondrial protein synthesis, chloramphenicol, T4-dependent induction of both enzyme synthesis and translatable carbamyl phosphate synthetase mRNA activity were repressed by 45-65%. The two measurements, synthesis in vivo and mRNA activity in vitro, were made on the same liver and correlated closely in their response to chloramphenicol. The data suggest that a product of mitochondrial protein synthesis may be involved in mediating hormonal regulation of the nuclear gene coding for carbamyl phosphate synthetase.
D000818:Animals; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics*; D002701:Chloramphenicol / Q000494:pharmacology*; D004794:Enzyme Repression / Q000187:drug effects; D007814:Larva / Q000378:metabolism; D008025:Ligases / Q000235:genetics*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics*; D011892:Rana catesbeiana; D013974:Thyroxine / Q000494:pharmacology*
D012333:RNA, Messenger; D002701:Chloramphenicol; D008025:Ligases; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D013974:Thyroxine