The Role of Metallothionein in Oxidative Stress

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Microarray analysis of metallothioneins in human diseases AbstractMetallothioneins (MTs), low molecular mass cysteine-rich proteins, which are able to bind up to 20 monovalent and up to 7 divalent heavy metal ions are widely studied due to their functions in detoxification of metals, scavenging free radicals and cells protection against the oxidative stress. It was found that the loss of the protective effects of MT leads to an escalation of pathogenic processes and carcinogenesis. 3The most extensive area is MTs expression for oncological applications, where the information about gene patterns is helpful for the identification biological function, resistance to drugs and creating the correct chemotherapy. In other medical applications the effect of oxidative stress to cell lines exposed to heavy metals and hydrogen peroxide is studied as well as influence of drugs and cytokines on MTs expression and MTs expression in the adiposetissue. The precise detection of low metallothionein concentrations and its isoforms is necessary to understand the connection between quantity and isoforms of MTs to size, localization and type of cancer. This information is necessary for well-timed therapy and increase the chance to survival. Microarray chips appear as good possibility for finding all information about expression of MTs genes and isoforms not only in cancer, but also in other diseases, especially diabetes, obesity, cardiovascular diseases, ageing, osteoporosis, psychiatric disorders and as the effects of toxic drugs and pollutants, which is discussed in this review. List of abbreviations:HCC -hepatocellular carcinoma, HFD -high fat diet, MMP -matrix metalloproteinase, MT -metallothionein, MTF -metal transcription factor, MRE -metal responsive element, ROS -reactive oxygen species.

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“…1). Moreover, there is increasing number of papers aimed at describing the role of these proteins in anticancer therapy [5][6][7][8][9][10].…”

Section: Metallothioneinsmentioning

confidence: 99%

Microarray analysis of metallothioneins in human diseases—A review

Křížková

Kępińska

Emri

et al. 2016

Journal of Pharmaceutical and Biomedical Analysis

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“…Metallothioneins are cysteine rich, low molecular weight proteins that are localized between the internal and external membranes of the mitochondria and play a regulatory role in the metabolism of essential metals such as zinc and copper and may also have a preventive role against oxidative damage by scavenging reactive oxygen as well as nitrogen species [27,28]. Similarly to our findings, others have reported that down-regulation of MT is a frequent phenomenon during the development of steatohepatitis (alcoholic and non-alcoholic) [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Effects of Antihypertensive and Triglyceride‐lowering Agents on Hepatic Copper Concentrations in Rats with Fatty Liver Disease

Ackerman

Skarzinski

Grozovski

et al. 2014

Basic Clin Pharma Tox

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Copper deficiency had been suggested to link between fructose-enriched diet (FED) and the development of non-alcoholic fatty liver disease (NAFLD). In this study, we characterized changes in hepatic copper concentrations and hepatic oxidative milieu, in rats with the metabolic syndrome and NAFLD as a result of FED with pharmacological manipulations to reduce blood pressure or plasma triglycerides. Changes in plasma and hepatic copper concentrations were correlated with changes observed in the immunohistochemical hepatic expression of copper-zinc-superoxide dismutase (CuZnSOD; SOD1), metallothionein (MT) and nitrotyrosine (NITT). FED administration was associated with a 2.2-fold reduction in hepatic copper concentrations, a decrease in the hepatic SOD1 expression, disappearance of the hepatic MT expression and increase in the hepatic NITT expression. Bezafibrate administration restored the hepatic copper concentrations and the hepatic SOD1 expression to levels that were observed in the control rats. A significant positive correlation between hepatic copper concentrations and the values of hepatic SOD1 expression of each animal included in this study was found. Administration of either captopril or bezafibrate increased hepatic MT expression, however, to levels that were lower than those observed in the control group. Administration of either amlodipine, or captopril or bezafibrate to the FED rats, had no effect on hepatic NITT expression. NAFLD development in FED rats is associated with a decrease in hepatic copper concentrations that is associated with a decrease in the hepatic SOD1 expression. Bezafibrate administration increases hepatic copper concentrations and restores the hepatic SOD1 expression.Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. The worldwide prevalence of NAFLD continues to increase with the growing obesity epidemic (reviewed in [1]). The most common risk factor for NAFLD is the presence of the metabolic syndrome that includes abdominal obesity and two or more of the following features: high blood pressure, elevated fasting plasma glucose and triglyceride levels, or low plasma HDL cholesterol levels. NAFLD is considered to be the hepatic manifestation of the metabolic syndrome (reviewed in [2]).Accumulating evidence from human and animal studies suggests that the increasing prevalence of NAFLD is associated with the increasing intake of simple sugars, especially fructose (reviewed in [3,4]). Consumption of fructose for long periods can predispose animals and individuals to hepatic fatty infiltration and the metabolic syndrome [3][4][5][6][7]. In recent years, the consumption of fructose, which is used in the food industry as a sweetener, has tremendously increased [4].As of now, multiple pathophysiological mechanisms including copper deficiency have linked between the increased fructose consumption and the development of NAFLD [4,[8][9][10][11][12].Copper is a trace element that is essential to the function of several enzymes involved in a vari...

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“…It is an essential mineral of biological and public health importance considered a life -saving commodity by the United Nations useful in a wide range of consumer goods, agricultural and industrial products (International Zinc Association, 2017). Zinc is a structural ion in transcription factors which is stored and transferred in metallothioneins -small cysteine-rich and heavy-metal-binding proteins which participate in an array of protective stress responses (Ruttkay-Nedecky et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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2017

EJERM

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An experiment was carried out to determine the ability of Pteridium aquilinum to accumulate zinc from solutions containing 10 mg/l zinc and 10mg/l of different inorganic and organic manures and to assess the effect of zinc on Clarias gariepinus. A 96-hour bioassay was carried out using Clarias gariepinus juveniles to determine the effect of its exposure on haematology and histology. The water and P.aquilinum were also analysed for zinc and other parameters. Variations were observed in haematological parameters such as Red blood cell, Packed cell volume, White blood cell, Haemoglobin and enzymes (Serum Glutamic -Oxaloacetic Transaminase, SGOT and Serum Glutamic -Pyruvic Transaminase, SGPT),while platelet and total protein showed no significant difference. Damage observed in organs included necrosis, cell individualization and disorganization and congestion.

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The Role of Metallothionein in Oxidative Stress

Cited by 705 publications

References 164 publications

Microarray analysis of metallothioneins in human diseases—A review

Microarray analysis of metallothioneins in human diseases—A review

Effects of Antihypertensive and Triglyceride‐lowering Agents on Hepatic Copper Concentrations in Rats with Fatty Liver Disease

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