Selenite restores Pax6 expression in neuronal cells of chronically arsenic-exposed Golden Syrian hamsters

Alain Aguirre-Arriaga; Adriana Sampayo-Reyes; Laura González-Escalante; Alba Hernández; Ricard Marcos; Fabiola Castorena-Torres; Gerardo Lozano-Garza; Reyes Taméz-Guerra; Mario Bermúdez de León

doi:10.18388/abp.2017_1607

Alain Aguirre-Arriaga Universidad Autónoma de Nuevo León, UANL, Fac. de Biología, Av. Universidad s/n Ciudad Universitaria, CP 66451, San Nicolás de los Garza, Nuevo León, Mexico.
Adriana Sampayo-Reyes Universidad Autónoma de Nuevo León, UANL, Fac. de Biología, Av. Universidad s/n Ciudad Universitaria, CP 66451, San Nicolás de los Garza, Nuevo León, Mexico.
Laura González-Escalante Department of Molecular Biology, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Av. 2 de abril 501, Col. Independencia, CP 64720, Monterrey, Nuevo León, Mexico
Alba Hernández Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Edifici Cn, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain CIBER Epidemiología y Salud Pública, ISCIII, Madrid, Spain
Ricard Marcos Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Edifici Cn, Campus de Bellaterra, 08193 Cerdanyola del Vallès, Spain CIBER Epidemiología y Salud Pública, ISCIII, Madrid, Spain
Fabiola Castorena-Torres Tecnológico de Monterrey, Escuela de Medicina, Dirección de Investigación e Innovación. CP 64710, Monterrey, Nuevo León, México.
Gerardo Lozano-Garza Department of Molecular Biology, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Av. 2 de abril 501, Col. Independencia, CP 64720, Monterrey, Nuevo León, Mexico
Reyes Taméz-Guerra Universidad Autónoma de Nuevo León, UANL, Fac. de Biología, Av. Universidad s/n Ciudad Universitaria, CP 66451, San Nicolás de los Garza, Nuevo León, Mexico.
Mario Bermúdez de León Department of Molecular Biology, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Av. 2 de abril 501, Col. Independencia, CP 64720, Monterrey, Nuevo León, Mexico http://orcid.org/0000-0002-0993-2969

DOI: https://doi.org/10.18388/abp.2017_1607

Keywords: arsenic, selenite, α-tocopherol, neuronal cells, hamster.

Abstract

Arsenic is a worldwide environmental pollutant that generates public health concerns. Various types of cancers and other diseases, including neurological disorders, have been associated with human consumption of arsenic in drinking water. At the molecular level, arsenic and its metabolites have the capacity to provoke genome instability, causing altered expression of genes. One such target of arsenic is the Pax6 gene that encodes a transcription factor in neuronal cells. The aim of this study was to evaluate the effect of two antioxidants, α-tocopheryl succinate (α-TOS) and sodium selenite, on Pax6 gene expression levels in the forebrain and cerebellum of Golden Syrian hamsters chronically exposed to arsenic in drinking water. Animals were divided into six groups. Using quantitative real-time reverse transcriptase (RT)-PCR analysis, we confirmed that arsenic downregulates Pax6 expression in nervous tissues by 53 ± 21% and 32 ± 7% in forebrain and cerebellum, respectively. In the presence of arsenic, treatment with α-TOS did not modify Pax6 expression in nervous tissues; however, sodium selenite completely restored Pax6 expression in the arsenic-exposed hamster forebrain (P = 0.394 vs. control group), but not the cerebellum. Although our results suggest the use of selenite to restore the expression of a neuronal gene in arsenic-exposed animals, its use and efficacy in the human population requires further studies.

Author Biography

Mario Bermúdez de León, Department of Molecular Biology, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Av. 2 de abril 501, Col. Independencia, CP 64720, Monterrey, Nuevo León, Mexico

Depto. de Biología Molecular

Full professor

References

Bach, J, Sampayo-Reyes, A, Marcos, R, Hernandez, A (2014) Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures. Archives of toxicology 88: 585-596. 10.1007/s00204-013-1151-0

Bellezza, I, Grottelli, S, Gatticchi, L, Mierla, AL, Minelli, A (2014) alpha-Tocopheryl succinate pre-treatment attenuates quinone toxicity in prostate cancer PC3 cells. Gene 539: 1-7. 10.1016/j.gene.2014.02.009

Bermingham, EN, Hesketh, JE, Sinclair, BR, Koolaard, JP, Roy, NC (2014) Selenium-enriched foods are more effective at increasing glutathione peroxidase (GPx) activity compared with selenomethionine: a meta-analysis. Nutrients 6: 4002-4031. 10.3390/nu6104002

Bhattacharjee, P, Banerjee, M, Giri, AK (2013) Role of genomic instability in arsenic-induced carcinogenicity. A review. Environment international 53: 29-40. 10.1016/j.envint.2012.12.004

Blake, JA, Ziman, MR (2014) Pax genes: regulators of lineage specification and progenitor cell maintenance. Development 141: 737-751. 10.1242/dev.091785

Chang, TI, Horal, M, Jain, SK, Wang, F, Patel, R, Loeken, MR (2003) Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects. Diabetologia 46: 538-545. 10.1007/s00125-003-1063-2

Chung, CJ, Pu, YS, Chen, YT, Su, CT, Wu, CC, Shiue, HS, Huang, CY, Hsueh, YM (2011) Protective effects of plasma alpha-tocopherols on the risk of inorganic arsenic-related urothelial carcinoma. The Science of the total environment 409: 1039-1045. 10.1016/j.scitotenv.2010.11.037

de Chevigny, A, Core, N, Follert, P, Gaudin, M, Barbry, P, Beclin, C, Cremer, H (2012) miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons. Nature neuroscience 15: 1120-1126. 10.1038/nn.3142

Duan, D, Fu, Y, Paxinos, G, Watson, C (2013) Spatiotemporal expression patterns of Pax6 in the brain of embryonic, newborn, and adult mice. Brain structure & function 218: 353-372. 10.1007/s00429-012-0397-2

Flora, SJ (1999) Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clinical and experimental pharmacology & physiology 26: 865-869.

Flora, SJ, Bhadauria, S, Pant, SC, Dhaked, RK (2005) Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats. Life sciences 77: 2324-2337. 10.1016/j.lfs.2005.04.016

Fraga, MF, Ballestar, E, Paz, MF, Ropero, S, Setien, F, Ballestar, ML, Heine-Suner, D, Cigudosa, JC, Urioste, M, Benitez, J, Boix-Chornet, M, Sanchez-Aguilera, A, Ling, C, Carlsson, E, Poulsen, P, Vaag, A, Stephan, Z, Spector, TD, Wu, YZ, Plass, C, Esteller, M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America 102: 10604-10609. 10.1073/pnas.0500398102

Fujimura, M, Usuki, F (2014) Low in situ expression of antioxidative enzymes in rat cerebellar granular cells susceptible to methylmercury. Archives of toxicology 88: 109-113. 10.1007/s00204-013-1089-2

Gailer, J (2009) Chronic toxicity of As(III) in mammals: the role of (GS)(2)AsSe(-). Biochimie 91: 1268-1272. 10.1016/j.biochi.2009.06.004

Hathcock, JN, Azzi, A, Blumberg, J, Bray, T, Dickinson, A, Frei, B, Jialal, I, Johnston, CS, Kelly, FJ, Kraemer, K, Packer, L, Parthasarathy, S, Sies, H, Traber, MG (2005) Vitamins E and C are safe across a broad range of intakes. The American journal of clinical nutrition 81: 736-745.

Jomova, K, Jenisova, Z, Feszterova, M, Baros, S, Liska, J, Hudecova, D, Rhodes, CJ, Valko, M (2011) Arsenic: toxicity, oxidative stress and human disease. Journal of applied toxicology : JAT 31: 95-107. 10.1002/jat.1649

Kaur, H, Mishra, D, Bhatnagar, P, Kaushik, P, Flora, SJS (2009) Co-administration of α-Lipoic Acid and Vitamin C Protects Liver and Brain Oxidative Stress in Mice Exposed to Arsenic Contaminated Water. Water Qual Expo Heal 1: 135-144. 10.1007/s12403-009-0013-8

Li, WH, Shi, YC, Tseng, IL, Liao, VH (2013) Protective efficacy of selenite against lead-induced neurotoxicity in Caenorhabditis elegans. PloS one 8: e62387. 10.1371/journal.pone.0062387

Livak, KJ, Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408. 10.1006/meth.2001.1262

Luo, JH, Qiu, ZQ, Zhang, L, Shu, WQ (2012) Arsenite exposure altered the expression of NMDA receptor and postsynaptic signaling proteins in rat hippocampus. Toxicology letters 211: 39-44. 10.1016/j.toxlet.2012.02.021

Medeiros, MC, Mello, A, Gemelli, T, Teixeira, C, de Almeida, M, de Andrade, RB, Wannmacher, CM, Guerra, RB, Gomez, R, Funchal, C (2012) Effect of chronic administration of the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on oxidative stress in different brain areas of rats. Neurochemical research 37: 928-934. 10.1007/s11064-011-0685-x

Nacher, J, Varea, E, Blasco-Ibanez, JM, Castillo-Gomez, E, Crespo, C, Martinez-Guijarro, FJ, McEwen, BS (2005) Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. Journal of neuroscience research 81: 753-761. 10.1002/jnr.20596

Needhamsen, M, White, RB, Giles, KM, Dunlop, SA, Thomas, MG (2014) Regulation of Human PAX6 Expression by miR-7. Evolutionary bioinformatics online 10: 107-113. 10.4137/EBO.S13739

Neuzil, J, Massa, H (2005) Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to pro-vitamin-to-vitamin conversion. Biochemical and biophysical research communications 327: 1024-1027. 10.1016/j.bbrc.2004.12.115

Neuzil, J, Wang, XF, Zhao, Y, Wu, K (2006) Vitamin E Analogs as Anticancer Agents. Press Taylor & Francis Group.

Norppa, H, Westermarck, T, Knuutila, S (1980) Chromosomal effects of sodium selenite in vivo. III. Aberrations and sister chromatid exchanges in Chinese hamster bone marrow. Hereditas 93: 101-105.

Prasad, KN, Kumar, B, Yan, XD, Hanson, AJ, Cole, WC (2003) Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review. Journal of the American College of Nutrition 22: 108-117.

Pritchard, C, Coil, D, Hawley, S, Hsu, L, Nelson, PS (2006) The contributions of normal variation and genetic background to mammalian gene expression. Genome biology 7: R26. 10.1186/gb-2006-7-3-r26

Rocha, RA, Gimeno-Alcaniz, JV, Martin-Ibanez, R, Canals, JM, Velez, D, Devesa, V (2011) Arsenic and fluoride induce neural progenitor cell apoptosis. Toxicology letters 203: 237-244. 10.1016/j.toxlet.2011.03.023

Sansom, SN, Griffiths, DS, Faedo, A, Kleinjan, DJ, Ruan, Y, Smith, J, van Heyningen, V, Rubenstein, JL, Livesey, FJ (2009) The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. PLoS genetics 5: e1000511. 10.1371/journal.pgen.1000511

Smith, J, Ladi, E, Mayer-Proschel, M, Noble, M (2000) Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell. Proceedings of the National Academy of Sciences of the United States of America 97: 10032-10037. 10.1073/pnas.170209797

Stankov, K, Bajin-Katic, K, Stanimirov, B, Karadzic, D, Kovacevic, Z (2007) Alpha-tocopheryl succinate (α-TOS) influences cell vitality and enzyme activity in Ehrlich ascites carcinoma cells. Arch Oncol 15: 65-68. 10.2298/AOO0704065S

Stoykova, A, Gruss, P (1994) Roles of Pax-genes in developing and adult brain as suggested by expression patterns. The Journal of neuroscience : the official journal of the Society for Neuroscience 14: 1395-1412.

Sturchio, E, Colombo, T, Boccia, P, Carucci, N, Meconi, C, Minoia, C, Macino, G (2014) Arsenic exposure triggers a shift in microRNA expression. The Science of the total environment 472: 672-680. 10.1016/j.scitotenv.2013.11.092

Tamura, K, Stecher, G, Peterson, D, Filipski, A, Kumar, S (2013) MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Molecular biology and evolution 30: 2725-2729. 10.1093/molbev/mst197

Tripathi, N, Kannan, GM, Pant, BP, Jaiswal, DK, Malhotra, PR, Flora, SJ (1997) Arsenic-induced changes in certain neurotransmitter levels and their recoveries following chelation in rat whole brain. Toxicology letters 92: 201-208.

Tyler, CR, Allan, AM (2013) Adult hippocampal neurogenesis and mRNA expression are altered by perinatal arsenic exposure in mice and restored by brief exposure to enrichment. PloS one 8: e73720. 10.1371/journal.pone.0073720

Tyler, CR, Allan, AM (2014) The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review. Current environmental health reports 1: 132-147. 10.1007/s40572-014-0012-1

Vaz, AR, Silva, SL, Barateiro, A, Falcao, AS, Fernandes, A, Brito, MA, Brites, D (2011) Selective vulnerability of rat brain regions to unconjugated bilirubin. Molecular and cellular neurosciences 48: 82-93. 10.1016/j.mcn.2011.06.008

Wang, X, Zhang, J, Zhao, L, Hu, S, Piao, F (2013) Effect of subchronic exposure to arsenic on levels of essential trace elements in mice brain and its gender difference. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 26: 123-131. 10.1007/s10534-012-9599-6

WHO (2010) Exposure to Arsenic : A Major Public Health Concern. . In Organization, W.H. (ed), http://www.who.int/ipcs/features/arsenic.pdf

Wlodraczyk, B, Bennett, GD, Calvin, JA, Craig, JC, Finnell, RH (1996) Arsenic-induced alterations in embryonic transcription factor gene expression: implications for abnormal neural development. Developmental genetics 18: 306-315. 10.1002/(SICI)1520-6408(1996)18:4<306::AID-DVG4>3.0.CO;2-D

Zhang, C, Li, S, Sun, Y, Dong, W, Piao, F, Piao, Y, Liu, S, Guan, H, Yu, S (2014) Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression. Toxicology letters 228: 260-269. 10.1016/j.toxlet.2014.05.007

Zhang, X, Huang, CT, Chen, J, Pankratz, MT, Xi, J, Li, J, Yang, Y, Lavaute, TM, Li, XJ, Ayala, M, Bondarenko, GI, Du, ZW, Jin, Y, Golos, TG, Zhang, SC (2010) Pax6 is a human neuroectoderm cell fate determinant. Cell stem cell 7: 90-100. 10.1016/j.stem.2010.04.017