Journal of Health Science
Online ISSN : 1347-5207
Print ISSN : 1344-9702
ISSN-L : 1344-9702
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Metal Response Element-binding Transcription Factor-1 Is Activated by Degradation of Metallothionein
Tomoki KimuraFumika OkumuraIkuyo OguroTsuyoshi NakanishiTomomichi SoneMasakazu IsobeKeiichi TanakaNorio Itoh
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2009 年 55 巻 1 号 p. 72-76

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Cytosolic zinc-binding protein, metallothionein (MT), is normally saturated with Zn. It is thought that Zn-saturated MT (Zn-MT) acts as a major intracellular Zn pool. Metal-response element-binding transcription factor-1 (MTF-1) plays an important role in Zn-mediated MT transcription. Here, we showed that degradation of Zn-MT activates MTF-1. We measured activated MTF-1 using an electrophoretic mobility shift assay. Interleukin-6 induced MT expression and increased MTF-1 activity. MTF-1 activation was not observed in MT-overexpressing cells. MT-dependent MTF-1 activation was observed only after treating MT-overexpressing cells with cycloheximide (CHX), a protein synthesis inhibitor. CHX-treatment increased the degradation/synthesis ratio of protein. An increase in the degradation/synthesis ratio for the MT protein is expected to increase the level of labile Zn and activate MTF-1. Recombinant MTF-1 was activated by H2O2 only in the presence of Zn-MT. Oxidative stress activated MTF-1 DNA-binding activity in primary cultured hepatocytes but not in MT-deficient hepatocytes. These findings suggest that degradation of Zn-MT activates MTF-1, and that MT plays an important role in zinc-mediated signal transduction.

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© 2009 by The Pharmaceutical Society of Japan
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