Metallothionein and its role in detoxification of heavy metals and predisposition to diseases

Czech version

Authors: M. Raudenská ¹; K. Šmerková ³; V. Tanhäuserová ¹; J. Gumulec ¹; M. Hlavna ¹; M. Sztalmachová ¹; L. Pácal ¹; P. Babula ²; V. Adam ³; T. Eckschlager ⁴; R. Kizek ³; M. Masařík ¹
Authors‘ workplace: Masarykova univerzita Brno, Lékařská fakulta, Ústav patologické fyziologie, Přednostka: prof. MUDr. Anna Vašků, CSc. ¹; Veterinární a farmaceutická univerzita v Brně, Ústav přírodních léčiv, Přednosta: doc. RNDr. Milan Žemlička, CSc. ²; Mendelova univerzita v Brně, Agronomická fakulta, Děkan: prof. Ing. Ladislav Zeman, CSc. ³; Univerzita Karlova v Praze, 2. Lékařská fakulta a Fakultní nemocnice Motol, Klinika dětské hematologie a onkologie, Přednosta: prof. MUDr. Jan Starý, DrSc. ⁴
Published in: Prakt. Lék. 2012; 92(6): 322-326
Category: Reviews

Overview

Heavy metals, including both essential and toxic heavy metals, are a major category of globally distributed environmental pollutants that negatively affect human health. Heavy metals have an ability to accumulate in the various tissues and become a part of the food chain. The most serious impact of toxic heavy metals is based on their interactions with many different enzymes and subsequently with many cellular processes. The significant variability between individual animal species and the considerable intra-species variability in heavy metal toxicity is well known. Different expression and function (sometimes caused by single nucleotide polymorphisms) of metal binding proteins such as metallothioneins or glutathione, which are useful at detoxification, may represent one of the reasons for inter- and intra-species variability. If the organism is not able to deal with the negative effects of heavy metals, a higher incidence of many diseases can occur. According to the various studies, the level of metallothionein (MT) expression and some single nucleotide polymorphisms (SNP) in the MT sequence were related to the risk of the genesis of different diseases and to the levels of heavy metals in various tissues. Recently, a significant relationship between SNP in the MT gene, diabetes type 2, cardiovascular diseases, and atherosclerosis has been identified. Some SNPs were responsible for higher levels of cadmium and lead in blood and kidneys, whereas zinc and copper levels were significantly decreased. The over-expression of MT can lead to the protection of cells, which should undergo apoptosis. The over-expression of MT has been observed in breast cancer, intestine and stomach cancer, bladder cancer, prostate cancer, as well as in head and neck cancer cells.

Key words:
heavy metals, metallothionein, polymorphisms, detoxification, metabolism, cancer, SNP.

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