Skip to main content
Log in

Selenium Deficiency-Induced Apoptosis of Chick Embryonic Vascular Smooth Muscle Cells and Correlations with 25 Selenoproteins

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Selenium deficiency is the major cause of exudative diathesis in chicks. Subcutaneous hemorrhage is one of the typical symptoms of the disease. However, the reason for the occurrence of blood exudation remains unknown. In the present study, the vascular smooth muscle cells (VSMCs) were isolated from 17-day-old broiler chick embryos. Cell viability, cell apoptosis, and intracellular reactive oxygen species level under different concentrations of selenium (0–0.9 μM) were investigated. The mRNA expression levels of 25 selenoproteins and apoptosis-related genes (p53, CytC, Caspase-3, Caspase-8, Bcl-2, and Bax) were also measured. Selenium deficiency significantly decreased cell viability and increased cell apoptosis (p < 0.05). Supplementation with selenium could alleviate these changes. In general, at all levels of selenium addition, Gpx1, Gpx3, Gpx4, SepW1, and Sep15 mRNAs were all highly expressed in VSMCs, whereas Gpx2, Dio1, SepN1, SelO, and SelPb were at lower levels. There was a high correlation between Gpx2, Gpx3, Gpx4, Dio1, Txnrd1, Txnrd2, and Txnrd3 gene expression. Additionally, Gpx3, Gpx4, Dio1, Txnrd1, Txnrd2, Txnrd3, SelS, and SelPb showed a strong negative correlation with pro-apoptotic gene Caspase-3 as well as a strong positive correlation with anti-apoptotic gene Bcl-2, especially SelI (r = 0.913 and r = 0.929, p < 0.01). These results suggest that selenium deficiency could induce VSMC apoptosis, and several selenoproteins may be involved in the development of apoptosis. Our findings provide information on the molecular mechanism of vascular injury by selenium deficiency.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wang X, Zhang W, Chen H, Liao N, Wang Z, Zhang X, Hai C (2014) High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS. Toxicol Lett 224(1):16–23

    Article  CAS  PubMed  Google Scholar 

  2. Wichtel J (1998) A review of selenium deficiency in grazing ruminants part 1: new roles for selenium in ruminant metabolism. Vet J 46(2):47–52

    CAS  Google Scholar 

  3. Yao H-D, Wu Q, Zhang Z-W, Zhang J-L, Li S, Huang J-Q, Ren F-Z, S-W X, Wang X-L, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigó R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300(5624):1439–1443

    Article  CAS  PubMed  Google Scholar 

  5. Wachi H, Seyama Y, Yamashita S, Tajima S (1995) Cell cycle-dependent regulation of elastin gene in cultured chick vascular smooth-muscle cells. Biochem J 309:575–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zhao X, Yao H, Fan R, Zhang Z, Xu S (2014) Selenium deficiency influences nitric oxide and selenoproteins in pancreas of chickens. Biol Trace Elem Res 161(3):341–349

    Article  CAS  PubMed  Google Scholar 

  7. Liang Y, Lin S-l, Wang C-w, H-d Y, Z-w Z, Xu S-w (2014) Effect of selenium on selenoprotein expression in the adipose tissue of chickens. Biol Trace Elem Res 160(1):41–48

    Article  CAS  PubMed  Google Scholar 

  8. Huang J-Q, Li D-L, Zhao H, Sun L-H, Xia X-J, Wang K-N, Luo X, Lei XG (2011) The selenium deficiency disease exudative diathesis in chicks is associated with downregulation of seven common selenoprotein genes in liver and muscle. J Nutr 141(9):1605–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vunta H, Belda BJ, Arner RJ, Channa Reddy C, Vanden Heuvel JP, Sandeep Prabhu K (2008) Selenium attenuates pro-inflammatory gene expression in macrophages. Mol Nutr Food Res 52(11):1316–1323

    Article  CAS  PubMed  Google Scholar 

  10. Halliwell B, Gutteridge J (1989) Protection against oxidants in biological systems: the superoxide theory of oxygen toxicity. Free radicals in biology and medicine. Claredon Press, Oxford

    Google Scholar 

  11. Zwolak I, Zaporowska H (2012) Selenium interactions and toxicity: a review. Biol Toxicol 28(1):31–46

    Article  CAS  Google Scholar 

  12. Gittenberger-de Groot AC, DeRuiter MC, Bergwerff M, Poelmann RE (1999) Smooth muscle cell origin and its relation to heterogeneity in development and disease. Arterioscl Throm Vas 19(7):1589–1594

    Article  CAS  Google Scholar 

  13. Hungerford J, Little C (1999) Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res 36(1):2–27

    Article  CAS  PubMed  Google Scholar 

  14. Palomino-Morales R, Alejandre MJ, Perales S, Torres C, Linares A (2014) Effect of PUFAs on extracellular matrix production and remodeling in vascular smooth muscle cell cultures in an atherosclerotic model. Eur J Lipid Sci Tech 116(11):1485–1495

    Article  CAS  Google Scholar 

  15. Safaralizadeh R, Nourizadeh M, Zare A, Kardar GA, Pourpak Z (2013) Influence of selenium on mast cell mediator release. Biol Trace Elem Res 154(2):299–303

    Article  CAS  PubMed  Google Scholar 

  16. Gao J, Zhang D, Zhang K, Liu M, Han Z, Li J (2012) Effects of selenium supplementation on expression of endothelin-1 and its receptors in pulmonary microvascular endothelial cells from chick embryos. Biol Trace Elem Res 150(1–3):173–177

    Article  PubMed  Google Scholar 

  17. Yu D, Z-w Z, H-d Y, Li S, Xu S-w (2014) Antioxidative role of selenoprotein W in oxidant-induced chicken splenic lymphocyte death. Biometals 27(2):277–291

    Article  CAS  PubMed  Google Scholar 

  18. Fang B, Zhang M, Tian M, Ren F (2015) Self-assembled β-lactoglobulin–oleic acid and β-lactoglobulin–linoleic acid complexes with antitumor activities. J Dairy Sci 98(5):2898–2907

    Article  CAS  PubMed  Google Scholar 

  19. Perales S, Alejandre MJ, Palomino-Morales R, Torres C, Linares A (2010) Influence of cholesterol and fish oil dietary intake on nitric oxide-induced apoptosis in vascular smooth muscle cells. Nitric Oxide 22(3):205–212

    Article  CAS  PubMed  Google Scholar 

  20. Saito Y, Yoshida Y, Akazawa T, Takahashi K, Niki E (2003) Cell death caused by selenium deficiency and protective effect of antioxidants. J Biol Chem 278(41):39428–39434

    Article  CAS  PubMed  Google Scholar 

  21. Hassan A, Ahn J, Suh Y, Choi YM, Chen P, Lee K (2014) Selenium promotes adipogenic determination and differentiation of chicken embryonic fibroblasts with regulation of genes involved in fatty acid uptake, triacylglycerol synthesis and lipolysis. J Nutr Biochem 25(8):858–867

    Article  CAS  PubMed  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(−Delta Delta C) method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  23. Liu H, Li X, Qin F, Huang K (2014) Selenium suppresses oxidative-stress-enhanced vascular smooth muscle cell calcification by inhibiting the activation of the PI3K/AKT and ERK signaling pathways and endoplasmic reticulum stress. J Biol Inorg Chem 19(3):375–388

    Article  CAS  PubMed  Google Scholar 

  24. Lin S-l, Wang C-w, Tan S-r, Liang Y, H-d Y, Z-w Z, Xu S-w (2014) Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids. Biol Trace Elem Res 161(3):263–271

    Article  CAS  PubMed  Google Scholar 

  25. Stadtman TC (2000) Selenium biochemistry: mammalian selenoenzymes. Ann N Y Acad Sci 899(1):399–402

    Article  CAS  PubMed  Google Scholar 

  26. Monsen ER (2000) Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. J Am Diet Assoc 100(6):637–640

    Article  CAS  PubMed  Google Scholar 

  27. Wang J, Qiao J, Zhao L, Li K, Wang H, Xu T, Tian Y, Gao M, Wang X (2007) Proliferation of pulmonary artery smooth muscle cells in the development of ascites syndrome in broilers induced by low ambient temperature. J Vet Med A 54(10):564–570

    Article  CAS  Google Scholar 

  28. Nunes VA, Gozzo AJ, Cruz-Silva I, Juliano MA, Viel TA, Godinho RO, Meirelles FV, Sampaio MU, Sampaio CA, Araujo MS (2005) Vitamin E prevents cell death induced by mild oxidative stress in chicken skeletal muscle cells. Comp Biochem Phys C 141(3):225–240

    Article  Google Scholar 

  29. Scheerer P, Borchert A, Krauss N, Wessner H, Gerth C, Höhne W, Kuhn H (2007) Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4). Biochemistry-US 46(31):9041–9049

    Article  CAS  Google Scholar 

  30. Chen J, Berry MJ (2003) Selenium and selenoproteins in the brain and brain diseases. J Neurochem 86(1):1–12

    Article  CAS  PubMed  Google Scholar 

  31. Loflin J, Lopez N, Whanger PD, Kioussi C (2006) Selenoprotein W during development and oxidative stress. J Inorg Biochem 100(10):1679–1684

    Article  CAS  PubMed  Google Scholar 

  32. Reeves MA, Hoffmann PR (2009) The human selenoproteome: recent insights into functions and regulation. Cell Mol Life Sci 66(15):2457–2478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yao H, Liu W, Zhao W, Fan R, Zhao X, Khoso PA, Zhang Z, Xu S (2014) Different responses of selenoproteins to the altered expression of selenoprotein W in chicken myoblasts. RSC Adv 4(109):64032–64042

    Article  CAS  Google Scholar 

  34. Han Y-H, Zhang Z-W, Su J, Zhang B, Li S, S-W X (2012) Effects of chicken selenoprotein W on H2O2-induced apoptosis in CHO-K1 cells. Biol Trace Elem Res 147(1–3):395–402

    Article  CAS  PubMed  Google Scholar 

  35. Skulachev VP (1998) Cytochrome c in the apoptotic and antioxidant cascades. FEBS Lett 423(3):275–280

    Article  CAS  PubMed  Google Scholar 

  36. Parihar A, Parihar MS, Nazarewicz R, Ghafourifar P (2010) Importance of cytochrome c redox state for ceramide-induced apoptosis of human mammary adenocarcinoma cells. BBA-Biomembranes 1800(7):646–654

    CAS  PubMed  Google Scholar 

  37. Horibata Y, Hirabayashi Y (2007) Identification and characterization of human ethanolaminephosphotransferase1. J Lipid Res 48(3):503–508

    Article  CAS  PubMed  Google Scholar 

  38. Wright MM, McMaster CR (2002) PC and PE synthesis: mixed micellar analysis of the cholinephosphotransferase and ethanolaminephosphotransferase activities of human choline/ethanolamine phosphotransferase 1 (CEPT1. Lipids 37(7):663–672

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by Chinese Natural Science Foundation: the Major International (Regional) Joint Research Program of China (No. 31320103920).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fazheng Ren.

Ethics declarations

Conflict of Interest

All authors declare that they have no conflict of interest.

Ethical Approval

The study followed all applicable international, national, and institutional guidelines for the care and use of animals. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice.

Electronic supplementary material

ESM 1

(DOC 79 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Huang, J., Zhang, H. et al. Selenium Deficiency-Induced Apoptosis of Chick Embryonic Vascular Smooth Muscle Cells and Correlations with 25 Selenoproteins. Biol Trace Elem Res 176, 407–415 (2017). https://doi.org/10.1007/s12011-016-0823-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-016-0823-z

Keywords

Navigation