Metallothionein polymorphisms in pathological processes

Raudenská, Martina; Gumulec, Jaromír; Podlaha, Ondřej; Sztalmachová, Markéta; Babula, Petr; Eckschlager, Tomáš; Adam, Vojtěch; Kizek, René; Masařík, Michal

doi:10.1039/c3mt00132f

Cited by 88 publications

(82 citation statements)

References 112 publications

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“…These results suggest that the contribution of MT to longevity is relatively high in prolongevity genes. Several polymorphisms have been detected in human MT genes and these are associated with pathological processes including aging, cancers, diabetes, and inflammation (Raudenska et al, 2014). Therefore, the decreased synthesis and defective function of MT proteins may be potential therapeutic targets of aging or life shortening in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain

Kadota

Aki

Toriuchi

et al. 2015

Experimental Gerontology

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Section: Introductionmentioning

confidence: 99%

Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain

Kadota

Aki

Toriuchi

et al. 2015

Experimental Gerontology

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“…Nevertheless, the tissue distribution can be well detected by immunohistochemistry, which was based for performing meta-analysis of metallothionein as an immunohistochemical marker of cancer [36]. Based on the published data it can be concluded that MT could be considered as a marker of tumour diseases, however, combination of mRNA and protein levels is needed [37,38]. Therefore, we aimed our attention at summarization of MT mRNA determination.…”

Section: Metallothionein Expressionmentioning

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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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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“…As mentioned previously, MTs are expressed by four different genes (MT1 , MT2 , MT3 , and MT4) with several isoforms [28,29]. Earlier data suggested that only two genes, namely MT1 and MT2 , are expressed in the presence of Pb; differences in MT3 expression were not associated with exposure to the metal, while, so far, the role of the MT4 gene is still not well understood [30,31].…”

Section: Resultsmentioning

confidence: 99%

Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal

Fernandes

Martins

Oliveira

et al. 2015

Public Health Genomics

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Lead (Pb) is a metal that accumulates in the human body, inducing several adverse health effects. One of the proteins responsible for the distribution of metal in the body is metallothionein (MT), which is expressed by different genes, and it is supposed that genetic variation in the genes that encode MTs may affect the Pb body burden. The present study aimed to evaluate the genetic effects of the polymorphism of MT2A (single nucleotide polymorphism rs10636; C→G) on blood Pb levels (BLL) of workers from car battery factories who are chronically exposed to the metal. In total, 221 men participated in the study; genomic DNA from whole blood was extracted, and genotyping of MT2A was performed by TaqMan assays; BLL were quantified by inductively coupled plasma mass spectrometry (ICP-MS). BLL were 25 ± 14 µg/dl (range 1.9-68); BLL were positively correlated with duration of work and smoking status. Individuals who carried at least one C allele had higher BLL than those with the GG genotype (β = -0.45; p = 0.025, multivariable linear regression analyses). Taken together, our data support the hypothesis that polymorphisms in genes related to the transport of Pb, such as MTs, may modulate the concentrations of the metal in the body and, consequently, adverse health effects induced by Pb exposure.

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Metallothionein polymorphisms in pathological processes

Cited by 88 publications

References 112 publications

Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain

Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain

Microarray analysis of metallothioneins in human diseases—A review

Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal

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