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Metallothionein
Published in Lars Friberg, Tord Kjellström, Carl-Gustaf Elinder, Gunnar F. Nordberg, Cadmium and Health: A Toxicological and Epidemiological Appraisal, 2019
Carl-Gustaf Elinder, Monica Nordberg
Shortly (2 to 3 hr) after parenteral administration of cadmium to rodents and mice, most of the cadmium in the liver is bound to high molecular weight proteins in the cytosol,1,38,59 but already after 8 hr more than 80% of the cadmium present in liver cell cytoplasma is bound to metallothionein.1,67 Although metallothionein is mainly present in the cytoplasm of renal and hepatic cells, induction of metallothionein results in its presence in cell nucleus also, as can be observed using immunohistochemical techniques.3,23 It has been suggested3,20 that there is a small amount of thionein (metallothionein without metal ions) present in the cytoplasma of the cells (Figure 5A). The thionein is bound to cytoplasmatic thionein mRNA and as a result of this binding the translation of mRNA to thionein is inhibited. When cadmium ions enter the cells, they will be picked up by the thionein, forming metallothionein and transported to the cell nucleus. At this stage there will be no inhibition of mRNA and translation to thionein will be started (Figure 5B). In the cell nucleus, metallothionein will possibly bind to DNA also and induce an increased production of thionein mRNA (Figure 5C). When all cadmium ions have been chelated by metallothionein, a small amount of thionein will again be capable of inhibiting cytoplasmatic mRNA (Figure 5D).
Genetic and Developmental Implications for Trace Metal metabolism from Mutant and Inbred Strains of Animals
Published in Owen M. Rennert, Wai-Yee Chan, Metabolism of Trace Metals in Man, 2017
Metallothionein is a metal-binding protein of unusual structure and importance in trace metal metabolism. It has been investigated most extensively for its role in cadmium detoxification,92,93 but it also plays a critical role in zinc and copper nutrition.94 The thioneins, as the proteins less the bound metals are called, are most unusual in that they contain 20 cysteine moieties among the 61 amino acid residues (molecular weight 6000). Over a dozen thioneins have been purified and sequenced for amino acids mostly from mammals but also from a fish, a crab, and from bread mold (Neurospora). Except for Neurospora (23 amino acids) the thionein is very similar in size and in amino acid composition and sequence. The protein has been highly conserved throughout evolution, the cysteine residues being almost invariable. All mammals examined possess two distinct gene products, two thioneins, which differ by only a few amino acids.
Copper-Thiolate Proteins (Metallothioneins)
Published in René Lontie, Copper Proteins and Copper Enzymes, 1984
Weser Ulrich, Hartmann Hans-Jürgen
It was demonstrated by X-ray photoelectron spectrometry that in the colorless Cu-thionein the sulfur was exclusively present as cysteine sulfur.13 The replacement of Cd and Zn by Cu(I) caused no oxidation of the RS- residues. The binding energy value remained at 161.9 eV. The aerobic displacement of Cd and Zn or treatment with H2O2 produced disulfide-bridged polymeric species. The disulfide sulfur was shifted to higher binding energies (sulfur 2p1/2.3/2 = 163.4 eV).
Mercury disrupts redox status, up-regulates metallothionein and induces genotoxicity in respiratory tree of sea cucumber (Holothuria forskali)
Published in Drug and Chemical Toxicology, 2020
Khaoula Telahigue, Imen Rabeh, Safa Bejaoui, Tarek Hajji, Salwa Nechi, Emna Chelbi, M’hamed El Cafsi, Nejla Soudani
Metallothioneins (MTs) are low-molecular-weight proteins that belong to the group of intracellular cysteine-rich, metal-binding proteins. They are highly inducible by a variety of stressors (Vasak and Meloni 2011). MTs are involved in different metabolic processes and functions including cellular antioxidant, essential metal homeostasis and heavy metal detoxification (Viarengo et al. 2000). Their use as biomarkers to assess metal contamination in both marine vertebrates and invertebrates has been confirmed (Bakiu et al. 2013). For Holothurians, and as far we know, our study is the first to investigate the MT synthesis changes in response to heavy metal contamination. Our data showed that treatment with high mercury concentrations (upper than 0.04 mg L−1) leads to an increase of MT contents in the respiratory tree tissue reflecting the impairment of the respiratory function in H. forskali. The increase in MT concentrations appeared to be resulting from the increased transcription as suggested by Kumar (2012). The ability of H. forskali to increase their MT concentrations seems to be a crucial cellular adaptive mechanism shielding the animal against mercury-induced toxicity. In this regard, previous study had shown that mercury stimulates MT synthesis through induction capacity of thionein synthesis and apoprotein-metal binding (Hamilton and Mehrle 1986). Functionally, the possible mechanism of MT protection against oxidative stress injury is due to the twenty cysteine residues which are involved in quenching hydroxyl and superoxide radicals as reported by Chiaverini and De Ley (2010).
The age-specific pathological changes of β-amyloid plaques in the cortex and hippocampus of APP/PS1 transgenic AD mice
Published in Neurological Research, 2022
Lu-Lu Xue, Li-Ren Huangfu, Ruo-Lan Du, Li Chen, Chang-Yin Yu, Liu-Lin Xiong, Ting-Hua Wang
Pathological alterations of β-amyloid plaques in the brains of AD and WT mice of different ages were observed and quantified using HE staining, Congo red staining and immunohistochemistry experiments in the study. Various components of tissue cells could be stained by HE staining which facilitates a comprehensive view of tissue structure [30]. Our results of HE staining showed that as age increased, the nuclei of cortical and hippocampal cells in AD mice were severely shrunken, with poorly defined structures, loose cell arrangement and irregular cell morphology. Congo red staining, considered as a diagnostic method for β-amyloidosis, could identify the β-amyloid plaque deposits in the brain tissues [31]. The outcome of Congo red staining showed that β-amyloid plaques began to appear in the brains of 6-month-old AD mice and fewer plaques in 9-month-old WT mice, and the number and area of red β-amyloid plaques gradually increased with age. Among all the age groups of AD mice, we noticed marked increases of β-amyloid plaques in both cortex and hippocampus of mice aged 6, 9, 12, 15 months compared to age-matched WT mice. Immunohistochemical staining enables intra-tissue localization and quantification of specific antigens in accordance with immunological principles to specifically reveal β-amyloid plaque deposition in brain tissues [32]. Interestingly, β-amyloid plaques were detected in the cortex and hippocampus of 6-month-old AD mice shown by Congo red staining while detected in the cortex and hippocampus of 4-month-old AD mice shown by immunohistochemical staining. Congo red staining is widely used in the diagnosis of amyloidosis. It is a highly sensitive diagnostic tool for diagnosing amyloidosis, and it is also the gold standard for detecting amyloid fibers (including amyloid deposits around Aβ42-enriched blood vessels, parenchyma and nucleus) [33,34]. However, a series of experiments showed that Congo red staining was insufficient to confirm the amyloid properties of protein aggregates. Congo red staining of amyloid also produces many false-positive results [35,36]. Fernandez-flores A. et al. examined 12 cases of skin amyloidosis and found that the positive rate of amyloid protein (Congo red and thionein T) detected by traditional methods was 87.50%, and the positive rate of immunohistochemistry was 100%, suggesting that immunohistochemistry was superior to other detection techniques for skin amyloid [37]. Our research results showed that the discrepancy between two different histological stainings indicated the higher specificity of immunohistochemical staining than Congo red staining. Thus, in the process of identifying the pathological changes of brain tissues with AD, both Congo red staining and immunohistochemical staining should be taken into consideration.