Metallothionein and its role in detoxification of heavy metals and predisposition to diseases
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 place of work:
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 the journal:
Prakt. Lék. 2012; 92(6): 322-326
Category:
Reviews
Summary
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.
Zdroje
1. Al-Saleh, I., Shinwari, N., Mashhour, A. et al. Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of healthy women. Int. J. Hyg. Environ. Health 2011, 214, p. 79–101.
2. Amiard, J.C., Amiard-Triquet, C., Barka, S. et al. Metallothioneins in aquatic invertebrates: their role in metal detoxification and their use as biomarkers. Aquat. Toxicol., 2006, 76, p. 160–202.
3. Cipriano, C., Malavolta, M., Costarelli, L., et al. Polymorphisms in MT1a gene coding region are associated with longevity in Italian Central female population. Biogerontology, 2006, 7, p. 357–365.
4. Cousins, R.J., Leinart, A.S. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1. FASEB J., 1988, 2, p. 2884–2890.
5. Dabrio, M., Rodríguez, A.R., Bordin, G., et al. Recent developments in quantification methods for metallothionein. J. Inorg. Biochem., 2002, 88, p. 123–134.
6. Ebadi, M., Leuschen, M.P., El Refaey, H., et al. The antioxidant properties of zinc and metallothionein. Neurochem. Int., 1996, 29, p. 159–166.
7. Ebert, M.P., Günther, T., Hoffmann, J., et al. Expression of metallothionein II in intestinal metaplasia, dysplasia, and gastric cancer. Cancer Res., 2000, 7, p. 1995–2001.
8. Fabrik, I., Kukačka, J., Adam, V., et al. Metalothionein a jeho vztah k protinádorové léčbě na bázi platinových komplexů. Prakt. lék., 2008, 88, s. 90–93.
9. Giacconi, R., Cipriano, C., Muti, E., et al. Novel -209A/G MT2A polymorphism in old patients with type 2 diabetes and atherosclerosis: relationship with inflammation (IL-6) and zinc. Biogerontology 2005, 6, p. 407–413.
10. Giacconi, R., Muti, E., Malavolta, M., et al. The +838 C/G MT2A polymorphism, metals, and the inflammatory/immune response in carotid artery stenosis in elderly people. Mol. Med., 2007, 13, p. 388–395.
11. Goulding, H., Jasani, B., Pereira, H., Reid A. Metallothionein expression in human breast cancer. Br J Cancer, 1995, 72, p. 968–972.
12. Gumulec, J., Masarik, M., Krizkova, S., et al. Insight to physiology and pathology of zinc(II) ions and their actions in breast and prostate carcinoma. Curr Med Chem., 2011, 18, p. 5041–5051.
13. Gumulec, J., Masarik, M., Krizkova, S., et al. Evaluation ofalpha-methylacyl-CoA racemase, metallothionein and prostate specific antigen as prostate cancer prognostic markers. Neoplasma, 2012, 59, p. 191–201.
14. Günes, C., Heuchel, R., Georgiev, O., et al. Embryonic lethality and liver degeneration in mice lacking the metal-responsive transcriptional activator MTF-1. EMBO J, 1998, 15, p. 2846–2854.
15. Hidalgo, J., Penkowa, M., Espejo, C., et al. Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation. Exp Biol Med (Maywood), 2006, 9, p. 1450–1458.
16. Horáková, Z., Tóthová, E., Salzman, R., a kol. Význam elevace hladin metalothioneinu v krvi u pacientů s nádory hlavy a krku. Otorinolaryng. a Foniat. /Prague/, 2008, 57, s. 90–97.
17. Hu, H. Bone lead as a new biologic marker of lead dose: recent findings and implications for public health. Environ. Health Perspect., 1998, 106, p. 961–967.
18. Chan, H.M., Cherian, M.G. Mobilization of hepatic cadmium in pregnant rats. Toxicol. Appl. Pharmacol., 1993, 120, p. 308–314.
19. Järup, L. Hazards of heavy metal contamination. Br. Med. Bull., 2003, 68, p. 167–182.
20. Kayaalti, Z., Mergen, G., Söylemezoğlu, T. Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population. Toxicol Appl Pharmacol., 2010, 245, p. 252–255.
21. Kayaalti, Z., Mergen, G., Söylemezoğlu, T. The potential effect of metallothionein 2A -5A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels. Toxicol Appl Pharmacol., 2011, 256, p. 1–7.
22. Kim, H.G., Kim, J.Y., Han, E.H., et al. Metallothionein-2A overexpression increases the expression of matrix metalloproteinase-9 and invasion of breast cancer cells. FEBS Lett, 2011, 585, p. 421–428.
23. Kita, K., Miura, N., Yoshida, M., et al. Potential effect on cellular response to cadmium of a single-nucleotide A /G polymorphism in the promoter of the human gene for metallothionein IIA. Hum. Genet., 2006, 120, p. 553–560.
24. Kizek, R., Vacek, J., Adam, V., a kol. Vztah metalothioneinu k rakovině a protinádorové léčbě. Klin. Biochem. Metab., 2004, 12, s. 72–78.
25. Liu, Y., Liu, J., Habeebu, S.M., et al. Metallothionein-I/II null mice are sensitive to chronic oral cadmium-induced nephrotoxicity. Toxicol. Sci., 2000, 57, p. 167–176.
26. Lu, J., Jin, T., Nordberg, G., Nordberg, M. Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers. Cell Stress Chaperones, 2001, 6, p. 97–104.
27. Masarik, M., Gumulec, J., Sztalmachova, M., et al. Isolation of metallothionein from cells derived from aggressive form of high-grade prostate carcinoma using paramagnetic antibody-modified microbeads off-line coupled with electrochemical and electrophoretic analysis. Electrophoresis, 2011, 32, p. 3576–3588.
28. Miura, N. Individual susceptibility to cadmium toxicity and metallothionein gene polymorphisms: with references to current status of occupational cadmium exposure. Ind. Health, 2009, 47, p. 487–494.
29. Prusa, R., Kizek, R., Trnkova, L., et al. Study of relationship between metallothionein and heavy metals by CPSA method. Clin Chem, 2004, 50, p. 28–29.
30. Puca, R., Nardinocchi, L., Bossi, G., et al. Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc. Exp Cell Res. 2009, 315, p. 67–75.
31. Qu, W., Diwan, B.A., Liu, J., et al. The metallothionein-null phenotype is associated with heightened sensitivity to lead toxicity and an inability to form inclusion bodies. Am. J. Pathol., 2002, 160, p. 1047–1056.
32. Ruiz-Riol, M., Martínez-Arconada, M.J., Alonso, N., et al. Overexpression of metallothionein I/II: a new feature of thyroid follicular cells in Graves’ disease. J Clin Endocrinol Metab, 2012, 97, p. 446–454.
33. Samson, S.L., Gedamu, L. Molecular analyses of metallothionein gene regulation. Prog. Nucleic Acid Res. Mol. Biol., 1998, 59, p. 257–288.
34. Sciavolino, P.J., Vilcek, J. Regulation of metallothionein gene expression by TNF-alpha and IFN-beta in human fibroblasts. Cytokine, 1995, 7, p. 242–250.
35. Siegsmund, M.J., Marx, C., Seemann, O., et al. Cisplatin-resistant bladder carcinoma cells: enhanced expression of metallothioneins. Urol Res., 1999, 27, p. 157–163.
36. Somji, S., Sens, M.A., Lamm, D.L., et al. Metallothionein isoform 1 and 2 gene expression in the human bladder: evidence for upregulation of MT-1X mRNA in bladder cancer. Cancer Detect Prev., 2001, 25, p. 62–75.
37. Tekin, D., Kayaaltı, Z., Aliyev, V., Söylemezoğlu, T. The effects of metallothionein 2A polymorphism on placental cadmium accumulation: is metallothionein a modifiying factor in transfer of micronutrients to the fetus? J. Appl. Toxicol., 2012, 32, p. 270–275.
38. Vasak, M. Advances in metallothionein structure and functions. J. Trace Elem. Med. Biol., 2005, 19, p. 13–17.
39. Waalkes, M.P., Harvey, M.J., Klaassen, C.D. Relative in vitro affinity of hepatic metallothionein for metals. Toxicol. Lett, 1984, 20, p. 33–39.
40. Yang, L., Li, H., Yu, T., et al. Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications. Am J Physiol Endocrinol Metab., 2008, 294, p. 987–992.
41. Yoshida, M., Ohta, H., Yamauchi, Y., et al. Age dependent changes in metallothionein levels in liver and kidney of the Japanese. Biol. Trace Elem. Res., 1998, 63, p. 167–175.
42. Zelená, J., Potěšil, D., Vacek, J., a kol. Metalothionein jako prognostický marker nádorového onemocnění. Klinická Onkologie, 2004, 17, s. 190–195.
43. Zitka, O., Krizkova, S., Huska, D., et al. Chip gel electrophoresis as a tool for study of matrix metalloproteinase 9 interaction with metallothionein. Electrophoresis, 2011, 32, p. 857–860.
Štítky
General practitioner for children and adolescents General practitioner for adultsČlánok vyšiel v časopise
General Practitioner
2012 Číslo 6
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Memantine Eases Daily Life for Patients and Caregivers
- Memantine in Dementia Therapy – Current Findings and Possible Future Applications
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
Najčítanejšie v tomto čísle
- Diseases of the knee cartilage and the repair options
-
Základy kognitivní, afektivní a sociální neurovědy
XIX. Mozek a stres - Correlation of alcohol consumption and cigarette smoking
- Metallothionein and its role in detoxification of heavy metals and predisposition to diseases