Post-transcriptional inhibition of ornithine decarboxylase induction by zinc in a difluoromethylornithine resistant cell line.
Addition of Zn2+ to cell medium inhibited the induction of ornithine decarboxylase (ODC) activity in ODC overproducing L1210-DFMOr cells. A significant effect was observed at a concentration as low as 0.01 mM, however, a more marked inhibition was caused by the addition of 0.1 mM Zn2+. The inhibition of the induction of ODC activity was accompanied by a proportional decrease in the content of immunoreactive ODC protein, whereas the level of ODC mRNA, determined by a solution hybridization RNase protection assay, was not affected significantly. Instead, some acceleration of ODC turnover was observed. The addition of 0.1 mM Co2+ or Mn2+, but not of other divalent metal ions, also inhibited ODC induction; differently from Zn2+ however, these metals affected cell viability and/or cell growth. Removal of endogenous Zn2+ by a chelator also provoked a strong decrease of ODC induction, which was reversed by Zn2+. However, addition of Zn2+ in excess of the chelator proved to be markedly inhibitory. These results indicate that both a restricted Zn2+ availability and an enhanced presence of the metal can inhibit the induction of ODC in L1210-DFMOr cells.
Flamigni
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Dipartimento di Biochimica, Università di Bologna, Italy.
Campana
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Carboni
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Rossoni
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Spampinato
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D000818:Animals; D002460:Cell Line / Q000187:drug effects; D004351:Drug Resistance; D000518:Eflornithine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D015032:Zinc / Q000494:pharmacology*
D012333:RNA, Messenger; D009955:Ornithine Decarboxylase; D015032:Zinc; D000518:Eflornithine