Differential sensitivity of rat liver and rat hepatoma cells to α-amanitin
| Autor: | Amal Boctor, Albert Grossman |
|---|---|
| Rok vydání: | 1973 |
| Předmět: |
Carcinoma
Hepatocellular Hydrocortisone Tritium Peptides Cyclic Biochemistry Tissue culture chemistry.chemical_compound Tyrosine aminotransferase Transcription (biology) RNA polymerase Animals Amanita phalloides Carbon Radioisotopes Enzyme inducer Uracil Uridine Polymerase Tyrosine Transaminase Cell Nucleus Orotic Acid Pharmacology chemistry.chemical_classification biology Nucleotides Basidiomycota Liver Neoplasms Adrenalectomy DNA-Directed RNA Polymerases Mycotoxins biology.organism_classification Molecular biology Rats Enzyme Liver chemistry Enzyme Induction Dactinomycin biology.protein Oligopeptides |
| Zdroj: | Biochemical Pharmacology. 22:17-28 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(73)90250-5 |
| Popis: | α-Amanitin, an inhibitor of RNA polymerase derived from the mushroom Amanita phalloides , was shown to be about five times more potent than actinomycin-D in inhibiting rat liver tyrosine aminotransferase induction by cortisol. Rat hepatoma cells grown in culture, however, were resistant to these inhibitory effects of α-amanitin, while actinomycin-D effectively inhibited enzyme induction in these cells. The insensitivity of the hepatoma cells could not be accounted for by: (a) specific binding of α-amanitin to fetal calf serum protein present in the tissue culture medium; (b) metabolic conversion of this bicyclic octapeptide to an active compound in rat liver which does not occur in hepatoma cells; or (c) rapid inactivation of this substance by the hepatoma cells. RNA polymerase studies with isolated nuclei indicated that inhibition of cortisol induction of rat liver tyrosine aminotransferase by α-amanitin was accompanied by an inhibition of Mn 2+ /(NH 4 ) 2 SO 4 -activated RNA polymerase. No effect on the Mg 2+ -activated polymerase was noted. Similar experiments with hepatoma cells, in conjunction with [ 14 C]-uracil and [ 3 H 5 ]-orotic acid uptake studies, indicated that the RNA polymerase of these cells was sensitive to α-amanitin only when the cell membrane was broken. The two major conclusions from these data are: (1) hepatoma cells are insensitive to α-amanitin because they are impermeable to this substance, and (2) the correlation between inhibition of the Mn 2+ /(NH 4 ) 2 SO 4 -activated RNA polymerase and inhibition of tyrosine aminotransferase induction by cortisol strongly suggests that modification of transcription by this hormone is the primary stimulus for increased synthesis of this enzyme. |
| Databáze: | OpenAIRE |
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