The effect of inhibitors of transcription and translation on basal and haem-induced tryptophan-2,3-dioxygenase activity in the rat liver.
The effect of actinomycin D and cycloheximide on basal tryptophan-2,3-dioxygenase (EC 1.13.11.11) activity in Wistar rat liver and on the enzyme activity induced by pretreatment with haemin was studied. Inhibition of either transcription or translation was accompanied by a reduction in tryptophan oxygenase activity, and this occurred more rapidly in the case of inhibition of translation. A 40% and 45% reduction in holoenzyme activity was found 2.5 and 6.5 h after introduction of cycloheximide and actinomycin D, respectively. Pretreatment with the antibiotics did not impair saturation of the apoenzyme by exogenous haem but haem induced tryptophan oxygenase activity was affected in various ways. Introduction of cycloheximide after haemin was accompanied by a rapid fall in the activity of both forms of the enzyme, but when transcription was inhibited under these conditions there was a subsequent increase in both holoenzyme activity and overall tryptophan oxygenase activity. The results support the concept that a regulatory pool of haem exists in hepatocytes and that haem is involved in both the activation and the degradation of tryptophan oxygenase.
Kaliman
P A
PA
Kharkov State University, Ukr.SSR.
Manandhar
S P
SP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology*; D006427:Hemin / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008099:Liver / Q000201:enzymology*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects; D014366:Tryptophan Oxygenase / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D003609:Dactinomycin; D006427:Hemin; D003513:Cycloheximide; D014366:Tryptophan Oxygenase