Preferential inhibition by proflavine of the hormonal induction of glutamine synthetase in embryonic neural retina.
The hormonal induction of glutamine synthetase (EC 6.3.1.2) in embryonic neural retina tissue in vitro is blocked preferentially and reversibly by proflavine (3,6-diaminoacridine) in the absence of cell or DNA replication; cell viability is not affected, and the synthesis of total cellular proteins and RNA is only slightly reduced. In the induction of this enzyme, there is a rapid increase in the synthesis and accumulation of the enzyme selectively elicited by the steroid inducer; for this effect, transcription is essential. Radioimmunochemical measurements have shown that proflavine inhibits induction by prevention of de novo synthesis of catalytically active and immunologically reactive glutamine synthetase protein. It does not measurably affect the uptake of the steroid inducer by the retina cells. Since the translation of this enzyme by preformed RNA templates is not stopped by proflavine, the inhibitory effect of proflavine on induction is apparently due to interference with transcriptional or pretranslational processes required for the provision of active transcripts for enzyme synthesis. The finding that proflavine inhibits preferentially a tissue-specific, inducible differentiation in postmitotic embryonic neural cells offers new approaches to the study of regulation of gene expression in eukaryotes.
D000166:Acridines / Q000494:pharmacology*; D000588:Amines / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival; D002642:Chick Embryo; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000096:biosynthesis; D003864:Depression, Chemical; D004586:Electrophoresis; D004790:Enzyme Induction / Q000187:drug effects; D005815:Genetic Code; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D007106:Immune Sera; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009924:Organ Culture Techniques; D012313:RNA / Q000096:biosynthesis; D011863:Radioimmunoassay; D012160:Retina / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D013698:Templates, Genetic; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000166:Acridines; D000588:Amines; D007106:Immune Sera; D009419:Nerve Tissue Proteins; D014316:Tritium; D012313:RNA; D004247:DNA; D005974:Glutamate-Ammonia Ligase; D013936:Thymidine