Superinduction of metallothionein I by inhibition of protein synthesis: role of a labile repressor in MTF-1 mediated gene transcription

Journal of Biochemical and Molecular Toxicology
Yongyi BiQiang Ma

Abstract

Induction of metallothioneins (MTs) through the metal-activated transcription factor-1 (MTF-1) provides a model response for analyzing transcriptional gene regulation by heavy metals. Here, we report inhibition of protein synthesis by cycloheximide (CHX) increases induction of Mt1 by approximately five-fold, a phenomenon designated as "superinduction." Characterization of superinduction revealed it is time- and concentration-dependent of CHX, requires the presence of an MTF-1 activator, and occurs at a transcriptional level, suggesting a labile repressor in the control of Mt1 induction. Genetic analyses using Mtf1 null cells and a metal response element (MRE)-driven reporter construct showed that superinduction of Mt1 is mediated through MTF-1 and MRE-dependent transcription. Analyses of intracellular zinc content by inductively coupled plasma emission spectroscopy and fluorescence imaging demonstrated that treatment with CHX alone or CHX plus an inducer does not increase the total zinc accumulation or the concentration of free zinc in cells under the conditions in which superinduction occurs. Moreover, superinduction was observed in cells cultured in a zinc-depleted medium, suggesting that superinduction does not involve eleva...Continue Reading

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Citations

Oct 1, 2010·American Journal of Physiology. Cell Physiology·Fang LiWenhui Hu
Jun 2, 2009·Biological & Pharmaceutical Bulletin·Jiaming YuSeiichiro Himeno
Dec 11, 2014·The Journal of Investigative Dermatology·Ichiro YajimaMasashi Kato
Jul 8, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Agnes Ferencz, Edit Hermesz
Nov 30, 2019·Current Pharmaceutical Biotechnology·Qingyun JiaLan Wang
Aug 29, 2017·BioFactors·Robertina GiacconiMauro Provinciali
Jun 3, 2008·Chemical Research in Toxicology·Xiaoqing HeQiang Ma
Aug 19, 2008·Chemical Research in Toxicology·Qiang Ma
May 10, 2021·Environmental Pollution·Milton TalukderJin-Long Li

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