Advertisement

Biological Trace Element Research

, Volume 189, Issue 2, pp 556–566 | Cite as

The Molecular Mechanisms of Protective Role of Se on the G0/G1 Phase Arrest Caused by AFB1 in Broiler’s Thymocytes

  • Ke Guan
  • Hang Li
  • Zhicai Zuo
  • Fengyuan Wang
  • Ping Hu
  • Xi PengEmail author
  • Jing FangEmail author
  • Hengmin Cui
  • Gang Shu
  • Ping Ouyang
Article
  • 70 Downloads

Abstract

This research was designed to explore the protective effects of sodium selenite on G0/G1 phase arrest induced by AFB1 in thymocytes of broilers. Two hundred eighty-eight Cobb broilers were divided into control group, + Se group (0.4 mg/kg Se), AFB1 group (0.6 mg/kg AFB1), and AFB1 + Se group (0.6 mg/kg AFB1 + 0.4 mg/kg Se). The results revealed that 0.4 mg/kg Se supplement in diets could improve the AFB1-induced histological lesions in the thymus consisting of the more vacuoles and nuclear debris in thymic cortical area. The results of flow cytometric detect showed that 0.4 mg/kg Se relieved the G0/G1 phase arrest caused by AFB1 in thymocytes. The results of transcription levels of ATM, p53, p21, p27, p15, p16, CyclinD1, CyclinE, Cdk6, Cdk2, and PCNA genes by qRT-PC, and protein expression level of PCNA by immunohistochemistry demonstrated that 0.4 mg/kg Se could reduce the adverse effects of AFB1 on these parameters. In conclusion, Se could relieve AFB1-induced G0/G1 phase arrest by p15 (or p16)-CyclinD1/Cdk6, ATM-p53-p21-CyclinE/Cdk2, p27-CyclinE/Cdk2 pathways.

Keywords

Sodium selenite AFB1 Cell cycle G0/G1 phase Thymus 

Notes

Funding Information

This work was supported by the program for Changjiang Scholars and University Innovative Research Team (PCSIRT) (No. 0848) and the Education Department of Sichuan Province (2012FZ0066) and (2013FZ0072).

Compliance with Ethical Standards

The use of broilers and all experimental procedures involving animals were approved by the Animal Health and Care Committee of Sichuan Agricultural University (approval No. SYXK2014-187).

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Chand N, Muhammad D, Durrani FR, Qureshi MS, Ullah SS (2011) Protective effects of milk thistle (Silybum marianum) against aflatoxin B1 in broiler chicks. Asian Australas J Anim Sci 24(7):1011–1018CrossRefGoogle Scholar
  2. 2.
    Meissonnier GM, Pinton P, Laffitte J, Cossalter AM, Gong YY, Wild CP, Bertin G, Galtier P, Oswald IP (2008) Immunotoxicity of aflatoxin B1: impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression. Toxicol Appl Pharmacol 231(2):142–149CrossRefGoogle Scholar
  3. 3.
    Hartley RD, Nesbitt BF, O'Kelly J (1963) Toxic metabolites of Aspergillus flavus. Nature 198(4885):1056–1058CrossRefGoogle Scholar
  4. 4.
    Lakkawar AW, Chattopadhyay SK, Johri TS (2004) Experimental aflatoxin B1 toxicosis in young rabbits-a clinical and patho-anatomical study. Anatol Stud 36(12):467–472Google Scholar
  5. 5.
    Fink-Gremmels J (2008) The role of mycotoxins in the health and performance of dairy cows. Vet J 176(1):84–92CrossRefGoogle Scholar
  6. 6.
    Richard JL (2007) Some major mycotoxins and their mycotoxicoses—an overview. Int J Food Microbiol 119(1–2):3–10CrossRefGoogle Scholar
  7. 7.
    Cancer IAFO (1993) Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. CarcinógenosGoogle Scholar
  8. 8.
    Raney VM, Harris TM, Stone MP (1993) DNA conformation mediates aflatoxin B1-DNA binding and the formation of guanine N7 adducts by aflatoxin B1 8,9-exo-epoxide. Chem Res Toxicol 6(1):64–68CrossRefGoogle Scholar
  9. 9.
    Bedard LL, Massey TE (2006) Aflatoxin B1-induced DNA damage and its repair. Cancer Lett 241(2):174–183CrossRefGoogle Scholar
  10. 10.
    Hartwell LH, Kastan MB (1994) Cell cycle control and cancer. Science 266(5192):1821–1828CrossRefGoogle Scholar
  11. 11.
    Schafer KA (1998) The cell cycle: a review. Vet Pathol 35(6):461–478CrossRefGoogle Scholar
  12. 12.
    Ezekiel CN, Alabi OA, Anokwuru CP, Oginni O (2011) Studies on dietary aflatoxin-induced genotoxicity using two in vivo bioassays. Arch Appl Sci Res 2:97–106Google Scholar
  13. 13.
    Jacotot E, Ferri KF, Kroemer G (2000) Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control. Pathol Biol (Paris) 48(3):271Google Scholar
  14. 14.
    Yang XJ, Zhang Z, Wang XC, Wang Y, Zhang XM, Lu HY, Wang SL (2013) Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage. Toxicol Appl Pharmacol 270(2):114–121.  https://doi.org/10.1016/j.taap.2013.04.005 CrossRefGoogle Scholar
  15. 15.
    Bianco G, Russo R, Marzocco S, Velotto S, Autore G, Severino L (2012) Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites aflatoxins M1 and M2. Toxicon 59(6):644–650.  https://doi.org/10.1016/j.toxicon.2012.02.010 CrossRefGoogle Scholar
  16. 16.
    Yu ZQ, Wang FY, Liang N, Wang CH, Peng X, Fang J, Cui HM, Muhammad JM, Lai WM (2015) Effect of selenium supplementation on apoptosis and cell cycle blockage of renal cells in broilers fed a diet containing aflatoxin B1. Biol Trace Elem Res 168(1):242–251.  https://doi.org/10.1007/s12011-015-0344-1 CrossRefGoogle Scholar
  17. 17.
    Yin H, Jiang M, Peng X, Cui HM, Zhou Y, He M, Zuo Z, Ouyang P, Fan JD, Fang J (2016) The molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum. Oncotarget 7(24):35592–35606.  https://doi.org/10.18632/oncotarget.9594 Google Scholar
  18. 18.
    Scott TR, Rowland SM, Rodgers RS, Bodine AB (1991) Genetic selection for aflatoxin B1 resistance influences chicken T-cell and thymocyte proliferation. Dev Comp Immunol 15(4):383–391.  https://doi.org/10.1016/0145-305X(91)90030-3 CrossRefGoogle Scholar
  19. 19.
    Bahari A, Mehrzad J, Mahmoudi M, Bassami MR, Dehghani H (2014) Cytochrome P450 isoforms are differently up-regulated in aflatoxin B1-exposed human lymphocytes and monocytes. Immunopharmacol Immunotoxicol 36(1):1–10CrossRefGoogle Scholar
  20. 20.
    Ellwanger JH, Franke SI, Bordin DL, Prá D, Henriques JA (2016) Biological functions of selenium and its potential influence on Parkinson's disease. An Acad Bras Cienc 88(3 Suppl):1655–1674CrossRefGoogle Scholar
  21. 21.
    Arthur JR, Mckenzie RC, Beckett GJ (2003) Selenium in the immune system. J Nutr 133(5 Suppl 1):1457S–1459SCrossRefGoogle Scholar
  22. 22.
    Zeng H (2002) Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr 132(4):674–679CrossRefGoogle Scholar
  23. 23.
    Yeh JY, Cheng LC, Liang YC, Ou BR (2009) Modulation of the arsenic effects on cytotoxicity, viability, and cell cycle in porcine endothelial cells by selenium. Endothelium 10(3):127–139CrossRefGoogle Scholar
  24. 24.
    Zhang SQ, Peng X, Fang J, Cui HM, Zuo ZC, Chen ZL (2014) Effects of aflatoxin B1 exposure and sodium selenite supplementation on the histology, cell proliferation, and cell cycle of jejunum in broilers. Biol Trace Elem Res 160(1):32–40.  https://doi.org/10.1007/s12011-014-0009-5 CrossRefGoogle Scholar
  25. 25.
    Hsieh CS, Lee HM, Lio CWJ (2012) Selection of regulatory T cells in the thymus. Nat Rev Immunol 12(3):157–167.  https://doi.org/10.1038/nri3155 CrossRefGoogle Scholar
  26. 26.
    Chen K, Shu G, Peng X, Fang J, Cui H, Chen J, Wang F, Chen Z, Zuo Z, Deng J (2013) Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B1. Food Chem Toxicol 59(3):446–454.  https://doi.org/10.1016/j.fct.2013.06.032 Google Scholar
  27. 27.
    Peng X, Bai SP, Ding XM, Zhang KY (2017) Pathological impairment, cell cycle arrest and apoptosis of thymus and bursa of Fabricius induced by aflatoxin-contaminated corn in broilers. Int J Environ Res Public Health 14(1):77.  https://doi.org/10.3390/ijerph14010077 CrossRefGoogle Scholar
  28. 28.
    Fang J, Yin H, Zheng Z, Zhu P, Peng X, Zuo Z, Cui H, Zhou Y, Ouyang P, Geng Y (2017) The molecular mechanisms of protective role of Se on the G2/M phase arrest of jejunum caused by AFB1. Biol Trace Elem Res 4:1–12Google Scholar
  29. 29.
    Liu C, Zuo Z, Zhu P, Zheng Z, Xi P, Jing F, Cui H, Yi Z, Ping O, Yi G (2017) Sodium selenite prevents suppression of mucosal humoral response by AFB1 in broiler’s cecal tonsil. Oncotarget 8(33):54215–54226Google Scholar
  30. 30.
    Dale N (1994) National research council nutrient requirements of poultry - ninth revised edition (1994). J Appl Poult Res 3(1):101–101.  https://doi.org/10.1093/japr/3.1.101 CrossRefGoogle Scholar
  31. 31.
    Kaoud HA (2015) Innovative methods for the amelioration of aflatoxin (AFB1) effect in broiler chicks. Sjar Net 1(2):19–24Google Scholar
  32. 32.
    Fang J, Cui H, Peng X, Chen Z, He M, Tang L (2011) Developmental changes in cell proliferation and apoptosis in the normal duck thymus. Anat Histol Embryol 40(6):457–465.  https://doi.org/10.1111/j.1439-0264.2011.01094.x CrossRefGoogle Scholar
  33. 33.
    Shini S, Kaiser P (2009) Effects of stress, mimicked by administration of corticosterone in drinking water, on the expression of chicken cytokine and chemokine genes in lymphocytes. Stress-The International Journal on the Biology of Stress 12(5):388–399.  https://doi.org/10.1080/10253890802526894 CrossRefGoogle Scholar
  34. 34.
    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(4):402–408.  https://doi.org/10.1006/meth.2001.1262 CrossRefGoogle Scholar
  35. 35.
    Nuttall KL, Allen FS (1984) Selenium detoxification of heavy metals: a possible mechanism for the blood plasma. Inorg Chim Acta 92(3):187–189CrossRefGoogle Scholar
  36. 36.
    Li W, Guo M, Liu Y, Mu W, Deng G, Li C, Qiu C (2016) Selenium induces an anti-tumor effect via inhibiting intratumoral angiogenesis in a mouse model of transplanted canine mammary tumor cells. Biol Trace Elem Res 171(2):371–379CrossRefGoogle Scholar
  37. 37.
    Tapiero H, Townsend DMTew KD (2003) The antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 57(3–4):134–144CrossRefGoogle Scholar
  38. 38.
    Piastowska-Ciesielska AW, Gajewska M, Wagner W, Domińska K, Ochędalski T (2014) Modulatory effect of selenium on cell-cycle regulatory genes in the prostate adenocarcinoma cell line ☆. J Appl Biomed 12(2):87–95CrossRefGoogle Scholar
  39. 39.
    Hao S, Hu J, Song S, Huang D, Xu H, Qian G, Huang K (2016) Selenium alleviates aflatoxin B1-induced immune toxicity through improving glutathione peroxidase 1 and selenoprotein S expression in primary porcine splenocytes. J Agric Food Chem 64(6):1385CrossRefGoogle Scholar
  40. 40.
    Chen K, Peng X, Fang J, Cui H, Zuo Z, Deng J, Chen Z, Geng Y, Lai W, Tang L (2014) Effects of dietary selenium on histopathological changes and T cells of spleen in broilers exposed to aflatoxin B1. Int J Environ Res Public Health 11(2):1904–1913CrossRefGoogle Scholar
  41. 41.
    Chen K, Fang J, Peng X, Cui H, Chen J, Wang F, Chen Z, Zuo Z, Deng J, Lai W (2014) Effect of selenium supplementation on aflatoxin B1-induced histopathological lesions and apoptosis in bursa of Fabricius in broilers. Food Chem Toxicol 74(74):91–97CrossRefGoogle Scholar
  42. 42.
    Liang N, Wang F, Peng X, Fang J, Cui H, Chen Z, Lai W, Zhou Y, Geng Y (2015) Effect of sodium selenite on pathological changes and renal functions in broilers fed a diet containing aflatoxin B1. Int J Environ Res Public Health 12(9):11196–11208CrossRefGoogle Scholar
  43. 43.
    Verma RJ (2004) Aflatoxin cause DNA damage. Int J Hum Genet 4(4):231–236CrossRefGoogle Scholar
  44. 44.
    Kurz EU, Lees-Miller SP (2004) DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst) 3(8–9):889–900.  https://doi.org/10.1016/j.dnarep.2004.03.029 CrossRefGoogle Scholar
  45. 45.
    Smorodinsky NI, Shiloh Y (2000) Enhanced phosphorylation of p53 by ATM in response to DNA damageGoogle Scholar
  46. 46.
    Elledge SJ (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274(5293):1664–1672.  https://doi.org/10.1126/science.274.5293.1664 CrossRefGoogle Scholar
  47. 47.
    Nakatsuka A, Wada J, Hida K, Hida A, Eguchi J, Teshigawara S, Murakami K, Kanzaki M, Inoue K, Terami T, katayama A, Ogawa D, Kagechika H, Makino H (2012) RXR antagonism induces G0/G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes. J Pathol 226(5):784–795.  https://doi.org/10.1002/path.3001 CrossRefGoogle Scholar
  48. 48.
    Orlando S, Gallastegui E, Besson A, Abril G, Aligué R, Pujol MJ, Bachs O (2015) P27Kip1 and p21Cip1 collaborate in the regulation of transcription by recruiting cyclin-Cdk complexes on the promoters of target genes. Nucleic Acids Res 43(14):6860–6873.  https://doi.org/10.1093/nar/gkv593 CrossRefGoogle Scholar
  49. 49.
    He G, Siddik ZH, Huang Z, Wang R, Koomen J, Kobayashi R, Khokhar AR, Kuang J (2005) Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities. Oncogene 24(18):2929–2943.  https://doi.org/10.1038/sj.onc.1208474 CrossRefGoogle Scholar
  50. 50.
    Sherr CJ (1994) G1 phase progression: cycling on cue. Cell 79(4):551–555.  https://doi.org/10.1016/0092-8674(94)90540-1 CrossRefGoogle Scholar
  51. 51.
    Bravo R, Frank R, Blundell PA, Macdonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature 326(6112):515–517.  https://doi.org/10.1038/326515a0 CrossRefGoogle Scholar
  52. 52.
    Li R, Shou W, Hannon GJ, Beach D, Stillman B (1994) Differential effects by thep21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 371(6497):534–537CrossRefGoogle Scholar
  53. 53.
    Cayrol C, Knibiehler M, Ducommun B (1998) p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells. Oncogene 16(3):311–320CrossRefGoogle Scholar
  54. 54.
    Kaushal N, Bansal MP (2007) Inhibition of CDC2/Cyclin B1 in response to selenium-induced oxidative stress during spermatogenesis: potential role of Cdc25c and p21. Mol Cell Biochem 298(1–2):139–150CrossRefGoogle Scholar
  55. 55.
    Gu X, Xu ZY, Zhu LY, Wang LF, Li K, Pei Q (2013) Dual control of Shuanghuang Shengbai granule on upstream and downstream signal modulators of CyclinD-CDK4/6 signaling pathway of cell cycle in Lewis-bearing mice with cyclophosphamide-induced myelosuppression. Oncotargets & Therapy 6:199–209.  https://doi.org/10.2147/OTT.S37407 Google Scholar
  56. 56.
    Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366(6456):704–707.  https://doi.org/10.1038/366704a0 CrossRefGoogle Scholar
  57. 57.
    Yan J, Tian J, Zheng Y, Han Y, Lu S (2012) Selenium promotes proliferation of chondrogenic cell ATDC5 by increment of intracellular ATP content under serum deprivation. Cell Biochem Funct 30(8):657–663CrossRefGoogle Scholar
  58. 58.
    Mei F, Tang J, Tang Y, Zhen Y, Sun H (2005) Effect of selenium on protein P16 expression in the testicle spermatogonium of rat with colon cancer induced by azoxymethane. Acta Anatomica Sinica 53(6):63018–63021(63014)Google Scholar
  59. 59.
    Su Y, Tang JM, Tang Y, Gao HY (2005) Effect of Na2SeO3 on experimental carcinogenesis of stomach and on p53 and p16 expression. Acta Anatomica Sinica 36(2):196–198Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary MedicineSichuan Agricultural UniversityChengduPeople’s Republic of China
  2. 2.College of Veterinary MedicineSichuan Agricultural UniversityChengduPeople’s Republic of China
  3. 3.College of Life SciencesChina West Normal UniversityNanchongPeople’s Republic of China

Personalised recommendations