Mechanism of Metallothionein Gene Activation Mediated by Heavy‐Metal Dependent Transcription Factor MTF‐1

Otsuka, Fuminori; Ohno, Sho; Suzuki, Kaoru; Takahashi, K.; Ohsawa, Motoyasu; Koizumi, Satoshi

doi:10.1002/chin.200733269

Cited by 4 publications

(4 citation statements)

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“…It has been shown that activated genes express apo-MT that binds zinc with high affinity (Rd = 10 -12 М). Under conditions of zinc insufficiency, metal-binding transcription factor-1 can form a complex with the Zn-corresponding inhibitor (MT transcription inhibitor) that blocks interactions between metal-binding transcription factor-1 and metal-binding elements [40][41][42].…”

Section: Functions Of Mts In the Cnsmentioning

confidence: 99%

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Ушакова

Kruchinenko

2009

Neurophysiology

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This review presents modern concepts on the structure and principles of classification of low-molecularweight proteins capable of binding with metal ions, metallothioneins (MTs). The mechanism underlying the binding of metals with these biopolymers is characterized; the main functions of MTs in the CNS, their role in defense reactions of neurons and other cells, as well as of those of the organism in general are reviewed.

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Section: Functions Of Mts In the Cnsmentioning

confidence: 99%

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Ушакова

Kruchinenko

2009

Neurophysiology

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“…Inducible MTs are the first detectable sign of exposure to heavy metals at the cellular level and may be used as biomarkers because there are probably constant levels of MTs in nonstressed cells [14,19,20]. Considerable differences in the content of MTs are related to species, tissues, age, nutrition, and other, unknown factors [21][22][23][24][25][26]. Although MTs have been identified in a broad range of species [18,27], there are no reports on MT levels in bats.…”

Section: Introductionmentioning

confidence: 99%

Heavy metals and metallothionein in vespertilionid bats foraging over aquatic habitats in the Czech Republic

Pikula

Zukal

Adam

et al. 2009

Enviro Toxic and Chemistry

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There has been growing interest in the study and conservation of bats throughout the world. Declines in their absolute numbers in recent decades are due, in part, to the fact that insectivorous bats may bioaccumulate toxic pollutants. The purpose of the present study was to quantify heavy metal concentrations in kidney, liver, and pectoral muscle samples in relation to metallothionein (MT) levels. In total, 106 bats belonging to 11 European species (i.e., Myotis myotis, Myotis daubentonii, Myotis brandtii, Myotis nattereri, Myotis emarginatus, Myotis mystacinus, Pipistrellus pipistrellus, Pipistrellus nathusii, Pipistrellus pygmaeus, Nyctalus noctulla, Eptesicus serotinus) were used for the study. The highest MT levels were found in Pipistrellus pipistrellus. High MT levels were also found in juvenile bats and aquatic-insect-foraging species. Cadmium was found only in the liver and kidney of Myotis myotis, except for a solitary finding in Pipistrellus pipistrellus. Myotis myotis juveniles had significantly higher liver and kidney Zn concentrations than adults. Interestingly, the liver Pb concentration was approximately two times higher in females than in males of Myotis myotis. The same gender difference was found for kidney Zn concentration in Pipistrellus pipistrellus. The present study confirms exposure of vespertilionid bats to toxic heavy metals (Pb, Cd) in the Czech Republic and provides data on the essential element Zn and the metal-binding protein MT in bats foraging over aquatic, aquatic and terrestrial, and terrestrial habitats.

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“…8) Transcriptional activation of the MT gene by heavy metals is mediated by a cis-acting DNA element, the metal response element (MRE). [9][10][11][12] MRE-binding transcription factor-1 (MTF-1) is a highly conserved zinc finger transcription factor that regulates the transcription of MT. 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.…”

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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Mechanism of Metallothionein Gene Activation Mediated by Heavy‐Metal Dependent Transcription Factor MTF‐1

Cited by 4 publications

References 1 publication

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Heavy metals and metallothionein in vespertilionid bats foraging over aquatic habitats in the Czech Republic

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

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