Identification of Metallothionein Gene in Human Plasma: A Molecular Analysis of Cadmium and Lead Pollution in Gas Station Environment

N. K. Dewi, A. Yuniastuti, A. M. A. Ahmed

Abstract

Metallothionein (MTs) is a protein that binds to metals, cysteine-rich and has low molecular weights. Metallothionein binds metals and has some essential cellular functions, such as transportation, storage, and metal detoxification. When metallic lead (Pb) and cadmium (Cd) are absorbed, it will immediately be bounded by metallothionein and transported by the blood to the liver. Metallothionein gene is encoded by MTs. This study aimed to identify the MTs gene in blood of fuel station workers which can further be used as a biomarker of the vulnerability of the body as a result of exposure to heavy metals like Pb and Cd in humans. This study was a cross-sectional study, conducted for 8 months and took place in Fuel Stations in the city of Semarang. Samples were fuel station workers who met the study criteria, they sought to fulfill as much as 52 samples. Blood of samples was taken approximately 5 ml and then the MT2 gene was analyzed using Polymerase Chain Reaction (PCR). The data were analyzed descriptively. The results showed that 96% of MT2 gene expression had a resemblance to normal human gene sequences by Blast GenBank. MT2 gene expression does not always reflect the accumulation of lead and cadmium in the blood of fuel station workers. The MT2 gene is likely to have a limitation when used as a biomarker for early detection of the heavy metals exposure in humans to determine the susceptibility of heavy metals exposure.

Keywords

biomarker, metallothioenian gene, lead, cadmium

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References

Baurand, P. E., Dallinger, R., Niederwanger, M., Capelli, N., Pedrini-Martha, V., & de Vaufleury, A. (2016). Differential Sensitivity of Snail Embryos to Cadmium: Relation to Age and Metallothionein Gene Expression. Environmental Science and Pollution Research, 23(4), 3062-3067.

Chen, L., Ma, L., Bai, Q., Zhu, X., Zhang, J., Wei, Q., ... & Liu, C. (2014). Heavy Metal-Induced Metallothionein Expression is Regulated by Specific Protein Phosphatase 2A Complexes. Journal of Biological Chemistry, 289(32), 22413–22426.

Chen, M. D., & Song, Y. M. (2009). Tissue Metallothionein Concentrations in Mice and Humans with Hyperglycemia. Biological Trace Element Research, 127(3), 251.

Claverie, J. M., & Notredame, C. (2003). Bioinformatics for Dummies. New York: Wiley Publishing, Inc.

Dziegiel, P., Pula, B., Kobierzycki, C., Stasiolek, M., & Podhorska-Okolow, M. (2016). Metallothioneins and Immune Function. In Metallothioneins in Normal and Cancer Cells (pp. 65-77). Springer, Cham.

Gillis, B. S., Arbieva, Z., & Gavin, I. M. (2012). Analysis of Lead Toxicity in Human Cells. BMC genomics, 13(1), 344.

Gonçalves, S. F., Davies, S. K., Bennett, M., Raab, A., Feldmann, J., Kille, P., ... & Bundy, J. G. (2016). Sub-Lethal Cadmium Exposure Increases Phytochelatin Concentrations in the Aquatic Snail Lymnaea Stagnalis. Science of the Total Environment, 568, 1054-1058.

Hadi, P. H. (2007). Transportasi Berwawasan Lingkungan. Semarang: Universitas Diponegoro.

Hanna-Attisha, M., LaChance, J., Sadler, R. C., & Champney Schnepp, A. (2016). Elevated Blood Lead Levels in Children Associated with the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response. American Journal Of Public Health, 106(2), 283-290.

Hanson. N.(2008). Does Fish Health Matter ? The Utility of Biomarkers in Fish for Environmental Assessment. Ph.D. Thesis Department of Plant and Environmental Sciences University of Gothenburg.

Hartini, E. (2010). Kadar Plumbum (Pb) dalam Darah pada Wanita Usia Subur di Daerah Pertanian. Jurnal Visikes, 9(2), 70-80.

Kayaaltı, Z., & Söylemezoğlu, T. (2010). The Polymorphism of Core Promoter Region on Metallothionein 2A-Metal Binding Protein in Turkish Population. Molecular Biology Reports, 37(1), 185-190.

Kayaaltı, Z., Aliyev, V., & Söylemezoğlu, T. (2011). The Potential Effect of Metallothionein 2A− 5 A/G Single Nucleotide Polymorphism on Blood Cadmium, Lead, Zinc and Copper Levels. Toxicology and Applied Pharmacology, 256(1), 1-7.

Klaassen, C. D., Liu, J., & Diwan, B. A. (2009). Metallothionein Protection of Cadmium Toxicity. Toxicology and Applied Pharmacology, 238(3), 215-220.

Krześlak, A., Forma, E., Jóźwiak, P., Szymczyk, A., Smolarz, B., Romanowicz-Makowska, H., ... & Bryś, M. (2014). Metallothionein 2A Genetic Polymorphisms and Risk of Ductal Breast Cancer. Clinical and experimental medicine, 14(1), 107-113.

Maret, W. (2011). Redox Biochemistry of Mammalian Metallothioneins. JBIC Journal of Biological Inorganic Chemistry, 16(7), 1079-1086.

Mehus, A. A., Muhonen, W. W., Garrett, S. H., Somji, S., Sens, D. A., & Shabb, J. B. (2014). Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-Rich Proteins. Molecular & Cellular Proteomics, 13, 1020–1033.

Meikawati, W., & Mumpuni, P. (2010). Hubungam antara Paparan Gas Buang Kendaraan (Pb) Dengan Kadar Hemoglobin dan Eritrosit Berdasarkan Lama Kerja pada Petugas Operator Wanita SPBU di Wilayah Semarang Selatan. Jurnal Kesehatan Masyarakat Indonesia, 6(2), 39-49.

Mifbakhuddin, M. W., & Mumpuni, P. (2010). Hubungan antara Paparan Gas Buang Kendaraan (Pb) Dengan Kadar Hemogoblin Dan Eritrosit Berdasarkan Lama Kerja Pada Petugas Operator Wanita SPBU di Wilayah Semarang Selatan. J Kesehat Masy Indones, 6(2), 41-5.

Miura, N. (2009). Individual Susceptibility to Cadmium Toxicity and Metallothionein Gene Polymorphisms: With References to Current Status of Occupational Cadmium Exposure. Industrial Health, 47(5), 487-494.

Nakazato, K., Tomioka, S., Nakajima, K., Saito, H., Kato, M., Kodaira, T., ... & Kodama, H. (2014). Determination of the Serum Metallothionein (MT) 1/2 Concentration in Patients with Wilson’s Disease And Menkes Disease. Journal of Trace Elements in Medicine and Biology, 28(4), 441-447.

Neal, A. P., & Guilarte, T. R. (2012). Mechanisms of Heavy Metal Neurotoxicity: Lead and Manganese. J Drug Metab Toxicol S, 5(2), 1-13.

Niederwanger, M., Calatayud, S., Zerbe, O., Atrian, S., Albalat, R., Capdevila, M., ... & Dallinger, R. (2017). Biomphalaria Glabrata Metallothionein: Lacking Metal Specificity of the Protein and Missing Gene Upregulation Suggest Metal Sequestration by Exchange Instead of through Selective Binding. International Journal of Molecular Sciences, 18(7), 1457.

Pedrini-Martha, V., Niederwanger, M., Kopp, R., Schnegg, R., & Dallinger, R. (2016). Physiological, Diurnal and Stress-Related Variability of Cadmium-Metallothionein Gene Expression in Land Snails. PloS one, 11(3), 1-7.

Ruttkay-Nedecky, B., Nejdl, L., Gumulec, J., Zitka, O., Masarik, M., Eckschlager, T., ... & Kizek, R. (2013). The Role of Metallothionein in Oxidative Stress. International Journal Of Molecular Sciences, 14(3), 6044-6066.

Ryvolova, M., Krizkova, S., Adam, V., Beklova, M., Trnkova, L., Hubalek, J., & Kizek, R. (2011). Analytical Methods for Metallothionein Detection. Current Analytical Chemistry, 7(3), 243-261.

Sakulsak, N. (2012). Metallothionein: An Overview on its Metal Homeostatic Regulation in Mammals. Int. J. Morphol, 30(3), 1007-1012.

Salice, C. J., Anderson, T. A., & Roesijadi, G. (2010). Adaptive Responses and Latent Costs of Multigeneration Cadmium Exposure in Parasite Resistant and Susceptible Strains of a Freshwater Snail. Ecotoxicology, 19(8), 1466-1475.

Sunoko, H. R., Hadiyarto, A., & Santoso, B. (2011). Dampak Aktivitas Transportasi Terhadap Kandungan Timbal (Pb) salam Udara Ambient Di Kota Semarang. J. Bioma, 1(2), 105-112.

Tekin, D., Kayaaltı, Z., Aliyev, V., & Söylemezoğlu, T. (2012). The Effects Of Metallothionein 2A Polymorphism on Placental Cadmium Accumulation: Is Metallothionein a Modifiying Factor in Transfer of Micronutrients to the Fetus?. Journal of Applied Toxicology, 32(4), 270-275.

Wang, W. C., Mao, H., Ma, D. D., & Yang, W. X. (2014). Characteristics, Functions, and Applications of Metallothionein in Aquatic Vertebrates. Frontiers in Marine Science, 1, 1-12.

World Health Organization. (2005). Bahaya Bahan Kimia pada Kesehatan Manusia dan Lingkungan. Diterjemahkan oleh Palupi Widyastuti. Jakarta: EGC.

Zatta, P. (2008). Metallothioneins in Biochemistry and Pathology. World Scientific.

Zein, M. S. A., & Prawiradilaga, D. M. (2013). DNA Barcode Fauna Indonesia. Jakarta: Prenada Media.

Zhang, B., Liu, Y. H., Wu, W. X., & Wang, Z. L. (2010). Molecular Phylogeny of Bactrocera Species (Diptera: Tephritidae: Dacini) Inferred from Mitochondrial Sequences of 16S rDNA and COI Sequences. Florida Entomologist, 93(3), 369-377.

DOI: https://doi.org/10.15294/jpii.v7i4.15487

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