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<main class="site-main" id="main"> <article id="post-88" class="post-88 post type-post status-publish format-standard has-post-thumbnail hentry category-metallothioneins tag-autoimmune-disorders tag-cadmium-toxicity tag-cytotoxicity tag-enzymes tag-health-disease tag-human-health tag-lipids tag-mercury tag-metallocene tag-metallothionein tag-metallothioneins tag-molecular-basis-of-inheritance tag-nephrotoxicity tag-physiological-metals tag-protein-phosphatase-2-pp2a tag-proteins tag-toxic-metals" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="800" height="419" src="https://toxicology.blog/archive/wp-content/uploads/2024/09/image-38-min.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" srcset="https://toxicology.blog/archive/wp-content/uploads/2024/09/image-38-min.jpg 800w, https://toxicology.blog/archive/wp-content/uploads/2024/09/image-38-min-300x157.jpg 300w, https://toxicology.blog/archive/wp-content/uploads/2024/09/image-38-min-768x402.jpg 768w" sizes="(max-width: 800px) 100vw, 800px" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">Understanding the Role of Metallothioneins in Human Health and Disease</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-09-24T18:14:44+05:30" itemprop="datePublished">September 24, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://toxicology.blog/archive/author/toxicology/" title="View all posts by toxicology" rel="author" itemprop="url"><span class="author-name" itemprop="name">toxicology</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <h3><b>Introduction</b></h3> <p><span style="font-weight: 400;">Metallocene ins (MTs) are low-molecular-weight proteins with a high proportion of cysteine residues involved in metal ion homeostasis, particularly zinc and copper, and the detoxification of toxic metals such as cadmium and mercury. Originally discovered more than sixty years ago, MT has been described for its capacity to sequester and manage metal ions by interaction with thiol groups in cysteine residues. So, the specific functions and diseases related to these five biochemicals are still the focus of debate. Here, the different aspects revolving around the versatility of MTs in metal transportation and the oxidative stress associated with diseases have been discussed.</span></p> <h3><b>The Biochemistry of Metallothioneins</b></h3> <p><span style="font-weight: 400;">MTs have a rich content of stray cysteine residues, which provide high-occurring constants for metal-ion interactions. They exist in various isoforms due to their differences in the ability to bind with metals and their localization in tissues. MTs chelate metal ions in metal-thiolate clusters; the physiological metals incorporated consist of zinc and copper, while the toxic metals include cadmium and mercury. Its biochemical characteristics are related to the structure-stability-function concept, and different MT versions can be quantified by the amount and type of the referred metal ions. This modulated structure enables MTs to change their mode of interaction and communication with other proteins and ligands necessary for their biological activities.</span></p> <h3><b>Role in Metal Homeostasis</b></h3> <p><span style="font-weight: 400;">In MTs, certain metal ions that are in excess in the cell are bound, while others are released to meet the requirements of enzymatic and other cellular processes. They operate as kinetic buffers that are active in maintaining proper metal ion concentrations, which are crucial in so many functions and yet so lethal if too high. Specifically, MTs are involved in the control of levels of zinc and copper, which are important for cell metabolism, enzymes, the stabilization of proteins, gene transcription, and translation. Rather, MTs sequester these metals, making them available in adequate concentrations when required, thus avoiding the unsettlement of the balance that can be brought about by the inhibition of enzymes or the creation of oxidative stress.</span></p> <h3><b>Metallothioneins and Oxidative Stress</b></h3> <p><span style="font-weight: 400;">MTs have antioxidant activity as they counteract the actions of free radicals and ROS and act to suppress the oxidation of cell structures, lipids, proteins, and DNA. Sequential redox cycling, which involves the conversion of MTs from the reduced to the oxidized state and vice versa, is possible due to the presence of cysteine thiol groups, and this increases the antioxidant capability of MTs. MTs are synthesized under stress conditions like metal and inflammation and oxidative stress/agents like metal-responsive transcription factor-1 and nuclear factor erythroid 2-derived factor. This induction enhances the MT’s capacity to remove toxic metals and ROS, leading to the prevention of oxidative damage.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://toxicology.blog/publication-trends/index/metallothioneins" target="_blank" title="metallothioneins - yearwise publication trends">metallothioneins</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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if (!statistics || Object.keys(statistics).length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var tableHTML = `<div class='pub-scroll'> <table class='tablediv' border='1' cellspacing='0' cellpadding='0'> <tr> <th>Year</th> <th>Publication Count</th> </tr>`; Object.entries(statistics).sort(([yearA], [yearB]) => yearB - yearA).forEach(([year, count]) => { const displayCount = count === 0 ? 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Adsorbing proteins or chelating agents, MTs bind to cadmium to help purge the body’s system. However, if the levels of cadmium consumed are high, then the MTs get saturated, and toxic effects on the kidneys or nephrotoxicity occur from the deposition of cadmium-bound MTs in the kidneys.</span></p> <h4><b>Cancer</b></h4> <p><span style="font-weight: 400;">MTs have dual functions in cancer; they prolong the endurance capacity of cancer cells to oxidative stress and promote the cancer cells’ survival rate during chemotherapy. On the other hand, it can be observed that MTs function as a tumor suppressor as they can influence metal ions and genes’ expression to control cancer increase and progression. MTs have a two-faced function in cancer because they can favor tumor cell growth but also decrease it.</span></p> <h4><b>Neurodegenerative Diseases</b></h4> <p><span style="font-weight: 400;">MTs enhance the survival of neurons in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease as they countercheck for metal ion imbalances and stresses caused by oxidations. They can detoxify toxic metals and ROS, thus protecting neurons and preventing apoptosis. MTs increase under stress conditions and promote neuron survival; therefore, they are considered for these disease therapy targets.</span></p> <h4><b>Diabetes and Cardiovascular Diseases</b></h4> <p><span style="font-weight: 400;">MTs are indicated in the management of diabetes and cardiovascular diseases since they have anti-oxidative stress and anti-inflammatory properties. They modulate redox signaling cascades and glucose homeostasis, thus affecting diseases and their progression and emanating complications. MTs can suppress the activation of proteins that generate inflammation and/or affect enzymes controlling glucose and insulin levels.</span></p> <h4><b>Autoimmune Disorders</b></h4> <p><span style="font-weight: 400;">If MT regulations are disturbed in autoimmune diseases, they lead to an improper immune response. MTs act on immune cells and regulate the production of cytokines; they also affect inflammation and immune tolerance. They inhibit T cell activation in its various aspects and regulate cytokine secretion, which makes them objects of interest for autoimmune disease treatment.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://toxicology.blog/recent-publications/index/metallothioneins" target="_blank" rel="noopener" title="metallothioneins - yearwise publication list">metallothioneins</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; 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publicationBlock.innerHTML = publicationHTML; resultsContainer.appendChild(publicationBlock); }); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://toxicology.blog/recent-publications/index/${key_replace}" target="_blank" title="${key} - publication list">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var recent_papers = [ { "title": "Pollution pressure drives microbial assemblages that improve the phytoremediation potential of heavy metals by Ricinus communis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38866993", "publishedDate": "2024" }, { "title": "Exposure to different cobalt chloride levels produces oxidative stress and lipidomic changes and affects the liver structure of Cyprinus carpio juveniles.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39117974", "publishedDate": "2024" }, { "title": "Multi-omic analysis of Huntington\\\\\\'s disease reveals a compensatory astrocyte state.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39112488", "publishedDate": "2024" }, { "title": "Metallothionein 3 Potentiates Pulmonary Artery Smooth Muscle Cell Proliferation by Promoting Zinc-MTF1-ATG5 Axis-mediated Autophagosome Formation.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38904023", "publishedDate": "2024" }, { "title": "Metal binding feature of copper\u2012induced metallothionein from freshwater crab Sinopotamon Henanense reveals its Cu\u2012thionein character.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38830441", "publishedDate": "2024" }, { "title": "Cellular Response of Adapted and Non-Adapted Strains to Europium Eu(III) Compounds.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38785768", "publishedDate": "2024" }, { "title": "Bacterial metallothionein, PmtA, a novel stress protein found on the bacterial surface of and involved in management of oxidative stress and phagocytosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38712943", "publishedDate": "2024" }, { "title": "A metallothionein from disk abalone (Haliotis discus discus): Insights into its functional roles in immune response, metal tolerance, and oxidative stress.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38777254", "publishedDate": "2024" }, { "title": "Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38169461", "publishedDate": "2024" }, { "title": "Effect of acute cadmium exposure on oxidative stress and antioxidant system of the scallop Aequipecten tehuelchus.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38387655", "publishedDate": "2024" }, { "title": "Reductive stress and cytotoxicity in the swollen river mussel (Unio tumidus) exposed to microplastics and salinomycin.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38462197", "publishedDate": "2024" }, { "title": "A Potential Involvement of Metallothionein in the Zinc Tolerance of Trichoderma harzianum: Experimental Findings.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38488956", "publishedDate": "2024" }, { "title": "ESI-MS analysis of Cu(I) binding to apo and Zn7 human metallothionein 1A, 2, and 3 identifies the formation of a similar series of metallated species with no individual isoform optimization for Cu(I).", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38503570", "publishedDate": "2024" }, { "title": "Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterised cadmium responsive transcript.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38549424", "publishedDate": "2024" }, { "title": "The influence of rainfall events on the toxicity of urban wastewaters to freshwater mussels Elliptio complanata.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38237842", "publishedDate": "2024" }, { "title": "Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38594765", "publishedDate": "2024" }, { "title": "Chronic effect of copper on biology, immunity, and biochemical assessment of Helicoverpa armigera (Lepidoptera; Noctuidae) in laboratory bioassays.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38567449", "publishedDate": "2024" }, { "title": "Chromiomics: Mechanisms of detoxification and tolerance in plants.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38631449", "publishedDate": "2024" }, { "title": "[Expressions of zinc homeostasis proteins, GPR39 and ANO1 mRNA in the sperm of asthenozoospermia patients and their clinical significance].", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39046409", "publishedDate": "2024" }, { "title": "Enhancing high-efficient cadmium biosorption of via cell surface displaying metallothionien CUP1.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39016212", "publishedDate": "2024" } ]; var keywordsArray = ["Metallothioneins","Metal Homeostasis","Oxidative Stress","Cadmium Toxicity","Cancer","Neurodegenerative Diseases","Diabetes","Cardiovascular Diseases","Autoimmune Disorders","Biomarkers"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h4><b>Metallothioneins as Biomarkers</b></h4> <p><span style="font-weight: 400;">MTs have been used as or have the potential for use as diagnostic or prognostic markers in several diseases. High levels of MT in blood or tissues show that one has undergone the process of exposure to heavy metals or has been stressed through the oxidation process. Some MT isoforms can be useful in the diagnosis of certain cancer types or neurodegenerative diseases, which will help in designing individual therapies. MT levels are useful in determining how metal ions and oxidative stress occur in tumor cells to help identify targeted therapies and early diagnosis.</span></p> <p><span style="font-weight: 400;">Projections Regarding Metallothionein Study Details New directions in the study are to define the MT roles in health and disease, utilizing the recent advancements in molecular biology and biotechnology. Molecular manipulations such as CRISPR/Cas9 engineering develop knockout models of MT deficiency to estimate the effects on trials. About MT-based therapeutics, gene therapy as well as small molecules stimulating MT activity are promising for the treatment of metal ion-associated and oxidative stress diseases. Such developments may cause remedies, enhancing the management of ailments, including HIV.</span></p> <h3><b>Conclusion</b></h3> <p><span style="font-weight: 400;"> MTs are involved and effective for metal ion transportation, oxidative stress protection, and disease mechanisms. Recent advancements in biochemical research show that there is still a need for research on the functions of these biochemicals in human health and disease. More studies will reveal other uses of MTs in the treatment and management of illnesses with disturbances in metal ion homeostasis and oxidative stress.</span></p> <p></p> <h3><b>References</b></h3> <ol> <li>Krezel, A. and Maret, W., 2021. <a href="https://pubs.acs.org/doi/full/10.1021/acs.chemrev.1c00371">The bioinorganic chemistry of mammalian metallothioneins.</a> <i>Chemical reviews</i>, <i>121</i>(23), pp.14594-14648.</li> <li>Nordberg, G.F., Bernard, A., Diamond, G.L., Duffus, J.H., Illing, P., Nordberg, M., Bergdahl, I.A., Jin, T. and Skerfving, S., 2018. <a href="https://pubs.acs.org/doi/full/10.1021/acs.chemrev.1c00371">Risk assessment of effects of cadmium on human health (IUPAC Technical Report).</a> <i>Pure and Applied Chemistry</i>, <i>90</i>(4), pp.755-808.</li> <li>Thévenod, F. and Wolff, N.A., 2016. <a href="https://academic.oup.com/metallomics/article/8/1/17/6000644">Iron transport in the kidney: implications for physiology and cadmium nephrotoxicity. </a><i>Metallomics</i>, <i>8</i>(1), pp.17-42.</li> <li>Fujishiro, H., Okugaki, S., Kubota, K., Fujiyama, T., Miyataka, H. and Himeno, S., 2009. <a href="https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/jat.1419">The role of ZIP8 down‐regulation in cadmium‐resistant metallothionein‐null cells.</a> <i>Journal of Applied Toxicology</i>, <i>29</i>(5), pp.367-373.</li> <li>Chang, X., Jin, T., Chen, L., Nordberg, M. and Lei, L., 2009. <a href="https://journals.sagepub.com/doi/abs/10.3181/0811-RM-336">Metallothionein I isoform mRNA expression in peripheral lymphocytes as a biomarker for occupational cadmium exposure.</a> <i>Experimental biology and medicine</i>, <i>234</i>(6), pp.666-672.</li> <li>Nordberg, G.F., Piscator, M. and Nordberg, M., 1971. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0773.1971.tb00660.x">On the distribution of cadmium in blood.</a> <i>Acta pharmacologica et toxicologica</i>, <i>30</i>(3‐4), pp.289-295.</li> <li>Nordberg, G.F., Piscator, M. and Lind, B., 1971. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0773.1971.tb00620.x">Distribution of Cadmium Among Protein Fractions of Mouse Liver1. </a><i>Acta Pharmacologica et Toxicologica</i>, <i>29</i>(5‐6), pp.456-470.</li> </ol> </div> <footer class="entry-meta" aria-label="Entry meta"> <span class="cat-links"><span class="gp-icon icon-categories"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M0 112c0-26.51 21.49-48 48-48h110.014a48 48 0 0143.592 27.907l12.349 26.791A16 16 0 00228.486 128H464c26.51 0 48 21.49 48 48v224c0 26.51-21.49 48-48 48H48c-26.51 0-48-21.49-48-48V112z" /></svg></span><span class="screen-reader-text">Categories </span><a href="https://toxicology.blog/archive/category/metallothioneins/" rel="category tag">Metallothioneins</a></span> <span class="tags-links"><span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" 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