Inhibition of δ-aminolevulinate synthetase induction by α-amanitin in avian liver cell cultures
Cytochrome P-450 Enzyme System
The induction of δ-aminolevulinate synthetase by the 5β-steroid etiocholanolone and the barbiturate derivative 2-allyl-2-isopropylacetamide was blocked by α-amanitin in avian hepatocyte cultures. δ-Aminolevulinate synthetase controls the initial and rate-limiting step of the porphyrin-heme pathway. α-Amanitin was demonstrated to be a potent inhibitor of the nucleoplasmic DNA-dependent RNA polymerase in chick embryo liver cells in culture. It is shown that nuclear RNA synthesis and nucleoplasmic RNA polymerase activities were inhibited by the toxin at an early time (6-6.5 h) in the induction period; whereas the nucleolar RNA polymerase was not inhibited. At this particular time of the induction period, enhancement of RNA synthesis was observed and was dependent on the effect of inducers; this enhancement was eliminated by α-amanitin. It is concluded that the increment of new RNA synthesized by the α-amanitin-sensitive nucleoplasmic RNA polymerase is required as one of the early steps in the induction process of δ-aminolevulinate synthetase, either as mRNA for the enzyme or for a specific protein required in the induction process. © 1974.
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