Skip to main content
Log in

Activation of Fas Receptors, Caspase-8 and Caspase-3 by Fluoride Ions in Rat Erythrocytes in vitro

  • Comparative and Ontogenic Biochemistry
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

The goal of the study was to demonstrate the ability of fluoride ions (F) to activate key components of the receptor-dependent apoptotic pathway, membrane Fas receptors, caspase-8 and caspase-3, in rat erythrocytes in vitro. Cells were incubated in the presence of increasing NaF concentrations (0.1–10 mM) for 1, 5 and 24 h. Caspase-8 and caspase-3 activities were assayed by flow cytometry, expression of Fas receptors by immunoblotting. It was found that the kinetics of stimulation of Fas receptors, caspases-8 and caspases-3 in rat erythrocytes by fluoride ions differs depending both on the fluoride concentration and exposure time. For instance, activation of caspases was observed as early as 1 h after incubation with fluoride, while treatment of erythrocytes with 5 mM NaF for 24 h increased the cell population with active caspases-8 and caspases-3 up to ca 15-16%. At the same time, expression of Fas receptors increased in a concentration-dependent manner only after 24 h of incubation with NaF. Thus, one of the mechanisms underlying premature death of rat erythrocytes induced by fluoride in vitro is the ability of the latter to stimulate messengers of the receptor-dependent apoptotic pathway. However, it is possible that caspase-8 and caspase-3 activation is, at least in part, independent of the membrane-associated mechanism of activation of Fas receptors.

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.

Similar content being viewed by others

References

  1. Fluoride in drinking water, Bailey, K., Chilton, J., Dahi, E., Lennon, M., Jackson, P., and Fawell, J., Eds., WHO Press, Switzerland, 2006.

  2. Pizzo, G., Piscopo, M.R., Pizzo, I., and Guiliana, G., Community water fluoridation and caries prevention: a critical review, Clin. Oral Invest., 2007, vol. 11, pp. 189–193.

    Article  Google Scholar 

  3. Peckham, S., Water fluoridation: a critical review of the physiological effects of ingestedfluoride as apub-lic health intervention, Sci. World J., 2014:293019. http://dx.doi.org/10.1155/2014/293019

    Google Scholar 

  4. Krishnamachari, K.A., Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease, Prog. Food Nutr. Sci., 1986, vol. 10, pp. 279–314.

    CAS  PubMed  Google Scholar 

  5. Bronckers, A.L., Lyaruu, D.M., and Den-Besten, P.K., The impact of fluoride on amelo-blasts and the mechanisms of enamel fluorosis, J. Dent. Res., 2009, vol. 88, pp. 877–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Reddy, D.R., Neurology of endemic skeletal fluorosis, Neurol. India, 2009, vol. 57, pp. 7–12.

    Article  PubMed  Google Scholar 

  7. Dec, K., Lukomska, A., Maciejewska, D., Jakubczyk, K., Baranowska-Bosiacka, I., Chlubek, D., Wasik, A., and Gutowska, I., The influence of fluorine on the disturbances of homeostasis in the central nervous system, Biol. Trace Elem. Res., 2017, vol. 177, pp. 224–234.

    Article  CAS  PubMed  Google Scholar 

  8. Barbier, O., Arreola-Mendoza, L., and Del Razo, L.M., Molecular mechanisms of fluoride toxicity, Chem.-Biol. Interact, 2010, vol. 188, pp. 319–333.

    Article  CAS  PubMed  Google Scholar 

  9. Agalakova, N.I. and Gusev, G.P., Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride, ISRN Cell Biol, 2012. ID 403835. http://dx.doi.org/10.5402/2012/403835

    Google Scholar 

  10. Ribeiro, D.A., Cardoso, C.M., Yujra, V.Q., De Barros Viana, M., Aguiar, O. Jr., Pisani, L.P., and Oshima, C.T.F. https://www.ncbi.nlm.nih.gov/pubmed/28870895_Fluoride induces apoptosis in mammalian cells: in vitro and in vivo studies, Anticancer Res., 2017, vol. 37, pp. 4767–4777.

    CAS  PubMed  Google Scholar 

  11. Bratosin, D., Estaquier, J., Petit, F., Arnoult, D., Quantannens, B., Tissier, J.P., Slomianny, C., Sartiaux, C., Alonso, C., Huart, J. J., Montreuil, J., and Ameisen, J.C., Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria, Cell Death Differ., 2001, vol. 8, pp. 1143–1156.

    Article  CAS  PubMed  Google Scholar 

  12. Berg, C.P., Engels, I.H., Rothbart, A., Lauber, K., Renz, A., Schlosser, S.F., Schulze-Osthoff, K., and Wesselborg, S., Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis, Cell Death Differ., 2001, vol. 8, pp. 1197–1206.

    Article  CAS  PubMed  Google Scholar 

  13. Mandal, D., Moira, P.K., and Basu, J., Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes, FEBS Lett., 2002, vol. 513, pp. 184–188.

    Article  CAS  PubMed  Google Scholar 

  14. Mandal, D., Baudin-Creuza, V., Bhattacharyya, A., Pathak, S., Delaunay, J., Kundu, M., and Basu, J., Caspase 3-mediated proteolysis of the N-terminal cytoplasmic domain of the human ery-throid anion exchanger 1 (band 3), J. Biol. Chem., 2003, vol. 278, pp. 52551–52558.

    Article  CAS  PubMed  Google Scholar 

  15. Mandal, D., Mazumder, A., Das, P., Kundu, M., and Basu, J., Fas, caspase 8-, and caspase- 3-de-pendent signaling regulates the activity of the ami-nophospholipid translocase and phosphatidylserine externalization in human erythrocytes, J. Biol. Chem., 2005, vol. 280, pp. 39460–39467.

    Article  CAS  PubMed  Google Scholar 

  16. Bratosin, D., Tcacenco, L., Sidoroff, M., Cotoraci, C., Slomianny, C., Estaquier, J., and Montreuil, J., Active caspases-8 and -3 in circulating human erythrocytes purified on immobilized annexin-V: a cytometric demonstration, Cytometry, 2009, vol. 75A, pp. 236–244.

    Article  Google Scholar 

  17. Agalakova, N.I. and Gusev, G.P., Fluorideinduced death of rat erythrocytes in vitro Toxicol. In Vitro, 2011, vol. 25, pp. 1609–1618.

    Article  CAS  Google Scholar 

  18. Agalakova, N.I. and Gusev, G.P., Excessive fluoride consumption leads to accelerated death of erythrocytes and anemia in rats, Biol. Trace Elem. Res., 2013, vol. 153, pp. 340–349.

    Article  CAS  PubMed  Google Scholar 

  19. Pietraforte, D., Matarrese, P., Straface, E., Gambardella, L., Metere, A., Scorza, G., Leto, T.L., Malorni, W., and Minetti, M., Two different pathways are involved in peroxynitrite-induced senescence and apoptosis of human erythrocytes, Free Radic. Biol. Med., 2007, vol. 42, pp. 202–214.

    Article  CAS  PubMed  Google Scholar 

  20. Mukherjee, K., Chowdhury, S., Mondal, S., Mandal, C., Chandra, S., Bhadra, R.K., and Mandal, C., 9-O-Acetylated GD3 triggers programmed cell death in mature erythrocytes, Biochem. Bio-phys. Res. Commun., 2007, vol. 362, pp. 651–657.

    Article  CAS  Google Scholar 

  21. Kriebardis, A.G., Antonelou, M.H., Stamoulis, K.E., Economou-Petersen, E., Margaritis, L.H., and Papassideri, I.S., Storage-dependent remodeling of the red blood cell membrane is associated with increased immunoglobulin G binding, lipid raft rearrangement, and caspase activation, Transfusion, 2007, vol. 47, pp. 1212–1220.

    Article  CAS  PubMed  Google Scholar 

  22. Agalakova, N.I. and Gusev, G.P., Fluoride induces oxidative stress and ATP depletion in the rat erythrocytes in vitro, Environ. Toxicol. Pharmacol., 2012, vol. 34, pp. 334–337.

    Article  CAS  PubMed  Google Scholar 

  23. Burgstahler, A.W., Recent research on fluoride and oxidative stress, Fluoride, 2009, vol. 42, pp. 73–74.

    Google Scholar 

Download references

Acknowledgements

This study was carried out on the equipment of the Center for Collective Use at Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to N. A. Agalakova.

Additional information

Russian Text © The Author(s), 2019, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2019, Vol. 55, No. 2, pp. 90–96.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Agalakova, N.A., Petrova, T.I. & Gusev, G.P. Activation of Fas Receptors, Caspase-8 and Caspase-3 by Fluoride Ions in Rat Erythrocytes in vitro. J Evol Biochem Phys 55, 97–103 (2019). https://doi.org/10.1134/S0022093019020029

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093019020029

Keywords

Navigation