Skip to main content

Advertisement

SpringerLink
Log in

High Concentration of Sodium Metasilicate Impairs Autophagic Flux and Induces Apoptosis in Human Umbilical Vein Endothelial Cells

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

Abstract

Silicon-doped materials have been widely used in bone regeneration research; however, a consensus on the safety range of silicon ions has not been reached and its toxicity mechanism remains to be further elucidated. This study aims to explore whether high level of sodium metasilicate can induce toxicity effect in human umbilical vein endothelial cells (HUVEC) and the role of autophagy and apoptosis in its toxic mechanism. HUVEC was treated with different level of high silicon and then investigated with respect to morphologic change, cell viability, immunofluorescence, the level of autophagy, and apoptosis-related protein. Moreover, bafilomycin A1 (Baf A1) was applied to detect whether autophagic flux is disrupted, and 3-methyladenine (3-MA, an autophagy inhibitor) was used to determine the relationship between autophagy and apoptosis. Results demonstrated that high-level silicon induced cell viability to decrease; LC3-II, p62, and apoptosis-related proteins were up-regulated after exposure to high-dose silicon (sodium metasilicate concentration more than 1 mM). There is no significant difference in LC3-II and p62 between Baf A1 and sodium metasilicate-exposed group. Besides, 3-MA further increased the apoptotic rate by inhibiting autophagy after high silicon exposure. Collectively, high concentration of silicon can impair autophagy and induce apoptosis in human umbilical vein endothelial cells, and autophagy may play a protective role in HUVEC apoptosis. Furthermore, silicon concentration used in HUVEC should not be more than 1 mM.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

Abbreviations

HUVEC:

Human umbilical vein endothelial cell

CCK-8:

Cell Counting Kit-8

BAX:

Bcl-2 associated X protein

PARP:

Poly ADP-ribose polymerase

LC3:

Light chain 3

3-MA:

3-Methyladenine

Baf A1:

Bafilomycin A1

ICP-AES:

Inductively coupled plasma atomic emission spectrometry

DAPI:

4′,6-Diamidino-2-phenylindole

References

  1. Carlisle EM (1970) Silicon: a possible factor in bone calcification. Science 167:279–280

    Article  CAS  PubMed  Google Scholar 

  2. Du M, Zhang J, Wang J, Hu L, Shan W (2012) Evaluation of silicon extract from leaves of phyllostachys edulis for topical anti-osteoporosis activity. In: World Automation Congress

    Google Scholar 

  3. Henstock JR, Canham LT, Anderson SI (2015) Silicon: the evolution of its use in biomaterials. Acta Biomater 11:17–26

    Article  CAS  PubMed  Google Scholar 

  4. Jugdaohsingh R (2007) Silicon and bone health. J Nutr Health Aging 11:99–110

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Macdonald HM, Hardcastle AC, Jugdaohsingh R, Fraser WD, Reid DM, Powell JJ Dietary silicon interacts with oestrogen to influence bone health: evidence from the Aberdeen Prospective Osteoporosis Screening Study. Accessed (3)

  6. Rodella LF, Bonazza V, Labanca M, Lonati C, Rezzani R (2014) A review of the effects of dietary silicon intake on bone homeostasis and regeneration. J Nutr Health Aging 18:820–826

    Article  CAS  PubMed  Google Scholar 

  7. KA H, PA R, N S and T B (2006) Effect of silicon level on rate, quality and progression of bone healing within silicate-substituted porous hydroxyapatite scaffolds. Biomaterials 27:5014–5026

  8. Dashnyam K, Elfiqi A, Buitrago JO, Perez RA, Knowles JC, Kim HW (2017) A mini review focused on the proangiogenic role of silicate ions released from silicon-containing biomaterials. J Tissue Eng 8 2041731417707339

  9. Han P, Wu C, Xiao Y (2013) The effect of silicate ions on proliferation, osteogenic differentiation and cell signalling pathways (WNT and SHH) of bone marrow stromal cells. Biomaterialsence 1:379–392

    CAS  Google Scholar 

  10. Bennett C, Samikkannu M, Mohammed F, Dietrich WD, Rajguru SM, Prasad A (2018) Blood brain barrier (BBB)-disruption in intracortical silicon microelectrode implants. Biomaterials 164:1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Biran R, Martin DC, Tresco PA (2005) Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp Neurol 195:115–126

    Article  CAS  PubMed  Google Scholar 

  12. Thorburn A (2017) Autophagy and disease. J Biol Chem 293 jbcR117.810739

  13. Marino G, Niso-Santano M, Baehrecke EH, Kroemer G (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:81–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Booth LA, Tavallai S, Hamed HA, Cruickshanks N, Dent P (2014) The role of cell signalling in the crosstalk between autophagy and apoptosis. Cell Signal 26:549–555

    Article  CAS  PubMed  Google Scholar 

  15. Liu X, Sun J (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-κB pathways. Biomaterials 31:8198–8209

    Article  CAS  PubMed  Google Scholar 

  16. Mladenovic Z, Johansson A, Willman B, Shahabi K, Bjorn E, Ransjo M (2014) Soluble silica inhibits osteoclast formation and bone resorption in vitro. Acta Biomater 10:406–418

    Article  CAS  PubMed  Google Scholar 

  17. Li Z, Liu F, Zhang L, Cao Y, Shao Y, Wang X, Jiang X, Chen Z (2018) Neuroserpin restores autophagy and promotes functional recovery after acute spinal cord injury in rats. Mol Med Rep 17:2957–2963

    CAS  PubMed  Google Scholar 

  18. Novosel EC, Kleinhans C, Kluger PJ (2011) Vascularization is the key challenge in tissue engineering. Adv Drug Deliv Rev 63:300–311

    Article  CAS  PubMed  Google Scholar 

  19. Santos MI, Unger RE, Sousa RA, Reis RL, Kirkpatrick CJ (2009) Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization. Biomaterials 30:4407–4415

    Article  CAS  PubMed  Google Scholar 

  20. Grellier M, Bordenave L, Amédée J (2009) Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering. Trends Biotechnol 27:562–571

    Article  CAS  PubMed  Google Scholar 

  21. Pruksa S, Siripinyanond A, Powell JJ, Jugdaohsingh R (2014) Silicon balance in human volunteers; a pilot study to establish the variance in silicon excretion versus intake. Nutr Metab (Lond) 11(1):4

    Article  CAS  Google Scholar 

  22. Li H, Ke X, Ni K, Kai L, Jiang C (2014) Silicate bioceramics enhanced vascularization and osteogenesis through stimulating interactions between endothelia cells and bone marrow stromal cells. Biomaterials 35:3803–3818

    Article  CAS  PubMed  Google Scholar 

  23. Zhai W, Lu H, Chen L, Lin X, Huang Y, Dai K, Naoki K, Chen G, Chang J (2012) Silicate bioceramics induce angiogenesis during bone regeneration. Acta Biomater 8:341–349

    Article  CAS  PubMed  Google Scholar 

  24. Duan J, Yu Y, Li Y, Yu Y, Sun Z (2013) Cardiovascular toxicity evaluation of silica nanoparticles in endothelial cells and zebrafish model. Biomaterials 34:5853–5862

    Article  CAS  PubMed  Google Scholar 

  25. Kim KH, Lee MS (2014) Autophagy--a key player in cellular and body metabolism. Nat Rev Endocrinol 10:322–337

    Article  CAS  PubMed  Google Scholar 

  26. Guo C, Yang M, Jing L, Wang J, Yu Y, Li Y, Duan J, Zhou X, Li Y, Sun Z (2016) Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling. Int J Nanomedicine 11:5257–5276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang J, Yu Y, Lu K, Yang M, Li Y, Zhou X, Sun Z (2017) Silica nanoparticles induce autophagy dysfunction via lysosomal impairment and inhibition of autophagosome degradation in hepatocytes. Int J Nanomedicine 12:809–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Asweto CO, Wu J, Alzain MA, Hu H, Andrea S, Feng L, Yang X, Duan J, Sun Z (2017) Cellular pathways involved in silica nanoparticles induced apoptosis: a systematic review of in vitro studies. Environ Toxicol Pharmacol 56:191–197

    Article  CAS  PubMed  Google Scholar 

  29. Nakamura S, Yoshimori T (2017) New insights into autophagosome-lysosome fusion. J Cell Sci 130:1209–1216

    Article  CAS  PubMed  Google Scholar 

  30. Mukhopadhyay S, Panda PK, Sinha N, Das DN, Bhutia SK (2014) Autophagy and apoptosis: where do they meet? Apoptosis 19:555–566

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate the instruction work by professor Changsheng Liu and his fellow from East China University of Science and Technology.

Funding

This work was supported by the Key Project of Natural Science Foundation of China (Grant No. 31330028)

Author information

Author notes

  1. Zheng Li, Shuhao Liu and Yuanwu Cao contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, China

    Zheng Li, Shuhao Liu, Yuanwu Cao, Tengfei Fu, Libo Jiang & Jian Zhang

Authors
  1. Zheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuhao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuanwu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tengfei Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Libo Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Zhang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Liu, S., Cao, Y. et al. High Concentration of Sodium Metasilicate Impairs Autophagic Flux and Induces Apoptosis in Human Umbilical Vein Endothelial Cells. Biol Trace Elem Res 191, 88–97 (2019). https://doi.org/10.1007/s12011-018-1608-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1608-3

Keywords

Search

Navigation