Mammalian metallothioneins: properties and functions

Babula, Petr; Masařík, Michal; Adam, Vojtěch; Eckschlager, Tomáš; Stiborová, Marie; Trnková, Libuše; Škutková, Helena; Provazník, Ivo; Hubálek, Jaromír; Kizek, René

doi:10.1039/c2mt20081c

Cited by 222 publications

(171 citation statements)

References 202 publications

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“…The co-correlation between hepatic concentrations of several of the metal species measured here suggests that their accumulation and/or retention in the liver may be linked, for example by interaction with a single class of binding site such as the metal-binding protein metallothionein (Andrews et al, 1996;Babula et al, 2012), which can be induced by glucocorticoids (Haq et al, 2003;Jacob et al, 1999). Notwithstanding the limited size of the data set, the results are sufficiently robust to suggest further investigation of the links between metal loading and feather CORT concentration are justified, particularly regarding the possibility of a functional relationship between the two.…”

Section: Variation In Feather Corticosterone Concentration With Exposmentioning

confidence: 89%

Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration

Strong

Pereira

Shore

et al. 2015

General and Comparative Endocrinology

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Article (refereed) -postprintStrong, Rebecca J.; Pereira, M. Gloria; Shore, Richard F.; Henrys, Peter A.; Pottinger, Tom G. 2015. Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration.Contact CEH NORA team at noraceh@ceh.ac.ukThe NERC and CEH trademarks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. feather CORT content and condition were observed in only tawny owl and kestrel. In sparrowhawks, feather CORT concentration was found to be positively related to the hepatic concentrations of five metals (Cd, Mn, Co, Cu, Mo) and the metalloid As. There was also a negative relationship between measures of condition and total hepatic metal concentration in males. The results suggest that some factors affecting CORT uptake by feathers remain to be resolved but feather CORT content from archived specimens has the potential to provide a simple effects biomarker for exposure to environmental contaminants.

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Section: Variation In Feather Corticosterone Concentration With Exposmentioning

confidence: 89%

Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration

Strong

Pereira

Shore

et al. 2015

General and Comparative Endocrinology

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“…[8] Under normal cellular conditions MT coordinates Zn II and Cu I ions. [9] In this state, MT is considered to act as a metallochaperone or storage protein, able to shuttle essential metals to apometalloenzymes.…”

Section: Introductionmentioning

confidence: 99%

Metalation Kinetics of the Human α‐Metallothionein 1a Fragment Is Dependent on the Fluxional Structure of the apo‐Protein

Irvine

Duncan

Gullons

et al. 2014

Chemistry A European J

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Mammalian metallothioneins are cysteine rich metal-binding proteins comprising, when fully metalated, two metal-binding domains: the α-domain binds with M4(II)S(Cys)11 stoichiometry and the β domain binds as M3(II)S(Cys)9 stoichiometry. While the fully metalated species have been widely studied, the metalation of the apoprotein is poorly understood. Key to a description of the metalation pathway(s) is the initial conformation of the apoprotein and the arrangement of the metal-coordinating cysteines prior to metalation. We report the effect of the ill-defined, globular structure of apoMT on metalation rates. In order to overcome the experimental limitations inherent in structural determinations of a fluxional protein we used a detailed analysis of the apo-α-metallothionein conformation based on the differential rate of cysteine modification with benzoquinone. The ESI mass spectral data show the presence of two distinct conformational families: one a folded conformational family at neutral pH and a second an unfolded family of conformations at low pH. The Cd(II) metalation properties of these two conformationally distinct families were studied using stopped-flow kinetics. Surprisingly, the unfolded apoprotein metalated significantly slower than the folded apoprotein, a result interpreted as being due to the longer time required to fold into the cluster structure when the fourth Cd(II) binds. These results provide the first evidence for the role of the structure of the apo-αMT in the metalation reaction pathways and show that cysteine modification coupled with ESI-MS can be used to probe structure in cysteine-rich proteins.

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“…Specifically in studies analyzing metal-induced cellular toxicity, the relative abundance of metallothioneins (MTs) [152] can be used as indicators of cellular responses to potentially toxic metals like copper, zinc, and cadmium [153,154]. However, in the given experimental context it has to kept in mind that MTs are multi-functional proteins and are also responsible for radical scavenging and physiological metal storage, and apparently also have a protective role in apoptosis [155].…”

Section: Cellular Protein Markersmentioning

confidence: 99%

Cell-based in vitro models in environmental toxicology: a review

Poteser¹

2017

Biomonitoring

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An analysis of biological effects induced by environmental toxins and exposure-related evaluation of potential risks for health and environment represent central tasks in classical biomonitoring. While epidemiological data and population surveys are clearly the methodological frontline of this scientific field, cellbased in vitro assays provide information on toxin-affected cellular pathways and mechanisms, and are important sources for the identification of relevant biomarkers. This review provides an overview on currently available in vitro methods based on cultured cells, as well as some limitations and considerations that are of specific interest in the context of environmental toxicology. Today, a large number of different endpoints can be determined to pinpoint basal and specific toxicological cellular effects. Technological progress and increasingly refined protocols are extending the possibilities of cell-based in vitro assays in environmental toxicology and promoting their increasingly important role in biomonitoring.

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Mammalian metallothioneins: properties and functions

Cited by 222 publications

References 202 publications

Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration

Feather corticosterone content in predatory birds in relation to body condition and hepatic metal concentration

Metalation Kinetics of the Human α‐Metallothionein 1a Fragment Is Dependent on the Fluxional Structure of the apo‐Protein

Cell-based in vitro models in environmental toxicology: a review

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