Chromium(VI) inhibits mouse metallothionein-I gene transcription by preventing the zinc-dependent formation of an MTF-1–p300 complex

Kimura, Toshikiro; Li, Yong; Okumura, Fumika; Itoh, Norio; Nakanishi, Takashi; Sone, Tomomichi; Isobe, Masakazu; Andrews, Glen K.

doi:10.1042/bj20081025

Cited by 29 publications

(18 citation statements)

References 31 publications

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“…To construct the secretory Cypridina luciferase expression plasmid for transient transfection study, chicken β-actin promoter was inserted into the multiple cloning site of pMCS- Cypridina Luc (Thermo Scientific, Waltham, MA, USA). Construction of MT-I-Luc was as previously described [28].…”

Section: Methodsmentioning

confidence: 99%

Cooperative Functions of ZnT1, Metallothionein and ZnT4 in the Cytoplasm Are Required for Full Activation of TNAP in the Early Secretory Pathway

et al. 2013

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The activation process of secretory or membrane-bound zinc enzymes is thought to be a highly coordinated process involving zinc transport, trafficking, transfer and coordination. We have previously shown that secretory and membrane-bound zinc enzymes are activated in the early secretory pathway (ESP) via zinc-loading by the zinc transporter 5 (ZnT5)-ZnT6 hetero-complex and ZnT7 homo-complex (zinc transport complexes). However, how other proteins conducting zinc metabolism affect the activation of these enzymes remains unknown. Here, we investigated this issue by disruption and re-expression of genes known to be involved in cytoplasmic zinc metabolism, using a zinc enzyme, tissue non-specific alkaline phosphatase (TNAP), as a reporter. We found that TNAP activity was significantly reduced in cells deficient in ZnT1, Metallothionein (MT) and ZnT4 genes (ZnT1 −/− MT −/− ZnT4 −/− cells), in spite of increased cytosolic zinc levels. The reduced TNAP activity in ZnT1 −/− MT −/− ZnT4 −/− cells was not restored when cytosolic zinc levels were normalized to levels comparable with those of wild-type cells, but was reversely restored by extreme zinc supplementation via zinc-loading by the zinc transport complexes. Moreover, the reduced TNAP activity was adequately restored by re-expression of mammalian counterparts of ZnT1, MT and ZnT4, but not by zinc transport-incompetent mutants of ZnT1 and ZnT4. In ZnT1 −/− MT −/− ZnT4 −/− cells, the secretory pathway normally operates. These findings suggest that cooperative zinc handling of ZnT1, MT and ZnT4 in the cytoplasm is required for full activation of TNAP in the ESP, and present clear evidence that the activation process of zinc enzymes is elaborately controlled.

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Section: Methodsmentioning

confidence: 99%

Cooperative Functions of ZnT1, Metallothionein and ZnT4 in the Cytoplasm Are Required for Full Activation of TNAP in the Early Secretory Pathway

et al. 2013

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“…In fact, most mammalian reporter plasmids are functional in DT40 cells (Buerstedde & Takeda, 2006). For example, the MT-luciferase reporter used to evaluate cytosolic zinc (Kimura et al, 2008) and the 5xATF6 luciferase used to monitor the UPR (Wang et al, 2000) are both effective in DT40 cells and can be used to assess changes in zinc transport (Ishihara et al, 2006;Jeong et al, 2012).…”

Section: Monitoring Cytosolic Zinc Levels and Zinc-related Homeostasimentioning

confidence: 99%

Methods to Evaluate Zinc Transport into and out of the Secretory and Endosomal–Lysosomal Compartments in DT40 Cells

Kambe

2014

Methods in Enzymology

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Zinc plays crucial roles in diverse biological processes. Recently, in addition to zinc mobilization into and out of the cell, zinc mobilization into and out of intracellular organelles, including the secretory and endosomal-lysosomal compartments, has received growing interest. In vertebrate cells, the Zrt/Irt-like proteins (ZIPs) and Zn transporters (ZnTs) are the two major families of zinc transport proteins involved in zinc mobilization across cellular membranes. Importantly, nearly half of them are localized to subcellular compartments. Thus, to elucidate the numerous zinc-related cellular events, understanding those ZIP and ZnT functions is critical. This chapter describes advanced methods used in our laboratory to examine zinc mobilization by them. Specifically, genetic and molecular approaches using chicken DT40 cells deficient in multiple ZIPs and ZnTs are described. Moreover, procedures to evaluate zinc-related phenotypes caused by the impairment of zinc mobilization into and out of the secretory and endosomal-lysosomal compartments are also described. These methods should be useful in characterizing the roles of zinc in diverse cellular events including endosomal signaling.

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“…17) Chromium(VI) pretreatment blocked the zinc-induced formation of the MTF-1-p300 complex (Fig. 2).…”

Section: Inhibitory Mechanisms Of Chromium(vi) On Mt Gene Transcriptionmentioning

confidence: 99%

“…The induction of MT gene transcription is attenuated by hexavalent chromium [chromium(VI)], 13,14) a toxic and carcinogenic heavy metal 15,16) that is present as an environmental pollutant. Chromium(VI) attenuates the induction of MT gene transcription by inhibiting the MTF-1-mediated transactivation, 14,17) which may contribute to its carcinogenicity. In this review, I briefly summarize the molecular mechanisms of the induction of MT transcription by zinc and other metals and its inhibition by chromium(VI), with a focus on mouse MT-I gene transcription.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Zinc-mediated Induction and Chromium(VI)-mediated Inhibition of Mouse Metallothionein-I Gene Transcription

Kimura

2010

JOURNAL OF HEALTH SCIENCE

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The expression of metallothionein (MT), a heavy-metal-binding protein, is induced by heavy metals such as zinc, copper, cadmium, and mercury. This induction of MT maintains zinc homeostasis and defends against toxic heavy metals by sequestering these metals and lowering their concentrations at critical intracellular sites. However, MT cannot bind chromium(VI), a heavy metal that has been known for over 100 years to be a human carcinogen. Chromium(VI) enters cells via the sulfate anion transporter system and is reduced to intermediate oxidation states, such as chromium(V) and chromium(IV), in the process of forming stable chromium(III) forms. Chromium(VI) is known to inhibit MT gene transcription, and recently my colleagues and I reported that chromium(VI) inhibits zinc-induced MT gene transcription by modifying the transactivation potential of metal response element-binding transcription factor-1 (MTF-1), a zinc-finger transcription factor. Inhibition of MT gene transcription may therefore be involved in the carcinogenicity of chromium(VI). In this review, I briefly summarize the molecular mechanisms of heavy metal-induced MT gene transcription and discuss the current status of research on chromium(VI) toxicity and chromium(VI)-mediated inhibition of MT gene transcription.

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Chromium(VI) inhibits mouse metallothionein-I gene transcription by preventing the zinc-dependent formation of an MTF-1–p300 complex

Cited by 29 publications

References 31 publications

Cooperative Functions of ZnT1, Metallothionein and ZnT4 in the Cytoplasm Are Required for Full Activation of TNAP in the Early Secretory Pathway

Cooperative Functions of ZnT1, Metallothionein and ZnT4 in the Cytoplasm Are Required for Full Activation of TNAP in the Early Secretory Pathway

Methods to Evaluate Zinc Transport into and out of the Secretory and Endosomal–Lysosomal Compartments in DT40 Cells

Molecular Mechanisms of Zinc-mediated Induction and Chromium(VI)-mediated Inhibition of Mouse Metallothionein-I Gene Transcription

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