Skip to main content
SpringerLink
Log in

Influence of iron-molybdenum nanocluster polyoxometalates on the apoptosis of blood leukocytes and the level of heat-shock proteins in the cells of thymus and spleen in rats

  • Published:
Nanotechnologies in Russia Aims and scope Submit manuscript

Abstract

We have studied the influence of iron-molybdenum nanocluster polyoxometalates on the organism of animals (rats) in order to determine the correlation between the exposure and changes at the cellular level in the blood and immune system. Single and repeated administrations of polyoxometalates lead to an increase in the amount of cells containing heat-shock proteins (HSPs) HSP60 and HSP70 not only in the spleen but also in the thymus, despite the blood–thymus barrier. The enhancement of both early and late apoptosis in leukocytes after the administration of 30 doses of polyoxometalates may result from the disruption of homeostasis in immunopoietic organs. No changes in the blood parameters indicative of inflammatory process or anemia are observed at any exposure. The increased level of HSPs in the cells of thymus and spleen and the absence of changes indicative of inflammation in the blood leucocytes, apparently, support the viability of cells in studied organs, since no morphological disruptions are found in the thymus and the spleen.

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

Similar content being viewed by others

References

  1. A. Müller, E. Krickemeyer, H. Bögge, M. Schidtmann, and F. Peters, “Organizational forms of matter: an inorganic superfullerene and keplerate based on molybdenum oxide,” Angew. Chem. Int. 37, 3360–3363 (1998).

    Google Scholar 

  2. A. Müller, S. Sarkar, S. Q. Nazir Shah, H. Bögge, M. Schidtmann, Sarkar Shatarupa, P. Kögerler, B. Hauptfleisch, A. X. Trautwein, V. Schünemann, “Archimedian synthesis and magic numbers: ‘sizing’ giant molybdenum–oxide based molecular spheres of the keplerate type,” Angew. Chem., Int. Ed. Engl.} 38, 3238–3241 (1999).

    Article  Google Scholar 

  3. A. A. Ostroushko, I. F. Gette, I. G. Danilova, E. A. Mukhlynina, M. O. Tonkushina, and K. V. Grzhegorzhevskii, “Studies on the possibility of introducing iron-molybdenum buckyballs into an organism by electrophoresis,” Nanotechnol. Russ. 9, 586–591 (2014).

    Article  Google Scholar 

  4. A. A. Ostroushko, I. G. Danilova, I. F. Gette, and M. O. Tonkushina, “Behavior of associates of keplerate type porous spherical Mo72Fe30 clusters with metal cations in electric field driven ion transport,” Russ. J. Inorg. Chem. 60, 500–504 (2015).

    Article  Google Scholar 

  5. A. A. Ostroushko, I. F. Gette, S. Yu. Medvedeva, M. O. Tonkushina, I. G. Danilova, A. V. Prokof’eva, and M. V. Morozova, “Evaluation of the safety of ironmolybdenum nanocluster polyoxometalates intended for targeted delivery of drugs,” Vestn. Ural. Med. Akad. Nauki 34 (2), 107–110 (2011).

    Google Scholar 

  6. A. A. Ostroushko, I. G. Danilova, I. F. Gette, S. Yu. Medvedeva, M. O. Tonkushina, A. V. Prokofieva, and M. V. Morozova, “Study of safety of molybdenum and iron-molybdenum nanocluster polyoxometalates intended for targeter delivery of drugs,” J. Biomater. Nanobiotechnol., No. 2, 557–560 (2011).

    Article  Google Scholar 

  7. A. A. Ostroushko, I. F. Gette, S. Yu. Medvedeva, I. G. Danilova, E. A. Mukhlynina, M. O. Tonkushina, and M. V. Morozova, “Study of acute and subacute action of iron-molybdenum nanocluster polyoxometalates,” Nanotechnol. Russ. 8, 672–677 (2013).

    Article  Google Scholar 

  8. I. G. Danilova, I. F. Gette, S. Yu. Medvedeva, E. A. Mukhlynina, M. O. Tonkushina, and A. A. Ostroushko, “Changing the content of histone proteins and heatshock proteins in the blood and liver of rats after the single and repeated administration of nanocluster ironmolybdenum polyoxometalates,” Nanotechnol. Russ. 10, 820–826 (2015).

    Article  Google Scholar 

  9. N. L. Flaherty, A. Chandrasekaran, P. Peña Mdel, G. A. Roth, S. A. Brenner, T. J. Begley, and J. A. Melendez, “Comparative analysis of redox and inflammatory properties of pristine nanomaterials and commonly used semiconductor manufacturing nano-abrasives,” Toxicol Lett. 239, 205–215 (2015).

    Article  Google Scholar 

  10. H. S. Park, S. J. Kim, T. J. Lee, G. Y. Kim, E. Meang, J. S. Hong, S. H. Kim, S. B. Koh, S. G. Hong, Y. S. Sun, J. S. Kang, Y. R. Kim, M. K. Kim, J. Jeong, J. K. Lee, W. C. Son, and J. H. Park, “A 90-day study of subchronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in sprague dawley rats,” Int. J. Nanomed. 9, 93 (2014).

    Google Scholar 

  11. C. de Haar, I. Hassing, M. Bol, R. Bleumink, and R. Pieters, “Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice,” Clin. Exp. Allergy 36, 1469–1479 (2006).

    Article  Google Scholar 

  12. J. Chang, G. Ichihara, Y. Shimada, S. Tada-Oikawa, J. Kuroyanagi, B. Zhang, Y. Suzuki, R. Sehsah, M. Kato, T. Tanaka, and S. Ichihara, “Copper oxide nanoparticles reduce vasculogenesis in transgenic zebrafish through down-regulation of vascular endothelial growth factor expression and induction of apoptosis,” J. Nanosci. Nanotechnol. 15, 2140–2147 (2015).

    Article  Google Scholar 

  13. S. V. Rana, “Metals and apoptosis: recent developments,” J. Trace Elem. Med. Biol. 22, 262–284 (2008).

    Article  Google Scholar 

  14. T. Olszowski, I. Baranowska-Bosiacka, I. Gutowska, K. Piotrowska, K. Mierzejewska, J. Korbecki, M. Kurzawski, M. Tarnowski, and D. Chlubek, “The effects of cadmium at low environmental concentrations on THP-1 macrophage apoptosis,” Int. J. Mol. Sci. 16, 21410–21427 (2015).

    Article  Google Scholar 

  15. L. Pradhan, R. Srivastava, and D. Bahadur, “Enhanced cell apoptosis triggered by a multi modal mesoporous amphiphilic drug delivery system,” Nanotecnology 26, 475–501 (2015).

    Article  Google Scholar 

  16. C. L. Wang, X. H. Cai, L. J. Zhang, Z. M. He, F. Sheng, J. Cheng, Y. Zhang, and B. A. Chen, “Influence of Fe3O4 magnetic nanoparticles combined with As2O3 and adriamycin on raji cell apoptosis and autophagy,” Zhongguo Shi Yan Xue Ye Xue Za Zhi 23, 1318–1324 (2015).

    Google Scholar 

  17. V. R. Khan and I. R. Brown, “The effect of hyperthermia on the induction of cell death in brain, testis, and thymus of the adult and developing rat,” Cell Stress Chaperones, No. 1, 73–90 (2002).

    Article  Google Scholar 

  18. H. T. Belay and I. R. Brown, “Spatial analysis of cell death and Hsp70 induction in brain, thymus, and bone marrow of the hyperthermic rat,” Cell Stress Chaperones 8, 395–404 (2003).

    Article  Google Scholar 

  19. W. A. Houry, “Chaperone-assisted protein folding in the cell cytoplasm,” Curr. Protein Pept. Sci. 2, 227–244 (2001).

    Article  Google Scholar 

  20. K. H. Baek, H. Zhang, B. R. Lee, Y. G. Kwon, S. J. Ha, and I. A. Shin, “Small molecule inhibitor for ATPase activity of Hsp70 and Hsc70 enhances the immune response to protein antigens,” Sci. Rep. 5, 17642 (2015).

    Article  Google Scholar 

  21. H. H. Kampinga, J. Hageman, M. J. Vos, H. Kubota, R. M. Tanguay, E. A. Bruford, M. E. Cheetham, B. Chen, and L. E. Hightower, “Guidelines for the nomenclature of the human heat shock proteins,” Cell Stress Chaperones 14, 105–111 (2009).

    Article  Google Scholar 

  22. A. Stacchiotti, L. F. Rodella, F. Ricci, R. Rezzani, A. Lavazza, and R. Bianchi, “Stress proteins expression in rat kidney and liver chronically exposed to aluminium sulphate,” Histol. Histopathol. 21, 131–140 (2006).

    Google Scholar 

  23. X. Wang, M. Chen, J. Zhou, and X. Zhang, “HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (review),” Int. J. Oncol. 45, 18–30 (2014).

    Google Scholar 

  24. A. Budina-Kolomets, G. M. Balaburski, A. Bondar, N. Beeharry, T. Yen, and M. E. Murphy, “Comparison of the activity of three different HSP70 inhibitors on apoptosis, cell cycle arrest, autophagy inhibition, and HSP90 inhibition,” Cancer Biol. Ther. 15, 194–199 (2014).

    Article  Google Scholar 

  25. D. Kennedy, K. Mnich, and A. Samali, “Heat shock preconditioning protects against ER stress-induced apoptosis through the regulation of the BH3-only protein BIM,” FEBS Open Bio. 4, 813–821 (2014).

    Article  Google Scholar 

  26. G. S. Kumar, A. Kulkarni, A. Khurana, J. Kaur, and K. Tikoo, “Selenium nanoparticles involve HSP-70 and sIRT1 in preventing the progression of type 1 diabetic nephropathy,” Chem. Biol. Interact. 223C, 125–133 (2014).

    Article  Google Scholar 

  27. E-K. Kim, J. D. Park, S-Y. Shim, H- S. Kim, B. I. Kim, J-H. Choi, and J. E. Kim, “Effect of chronic hypoxia on proliferation, apoptosis, and HSP70 expression in mouse bronchiolar epithelial cells,” Physiol. Res. 55, 405–411 (2006).

    Google Scholar 

  28. S. Walter and J. Buchner, “Molecular chaperones - cellular machines for protein folding,” Angew Chem. Int. Ed. Engl. 41, 1098–1113 (2002).

    Article  Google Scholar 

  29. C. Grundtman, S. B. Kreutmayer, G. Almanzar, M. C. Wick, and G. Wick, “Heat shock protein 60 and immune inflammatory responses in atherosclerosis,” Arterioscler. Thromb. Vasc. Biol. 31, 960–968 (2011).

    Article  Google Scholar 

  30. Y. Vercoulen, N. H. van Teijlingen, I. M. de Kleer, S. Kamphuis, S. Albani, and B. J. Prakken, “Heat shock protein 60 reactive t cells in juvenile idiopathic arthritis: what is new?,” Arthritis Res. Ther. 11, 231 (2009).

    Article  Google Scholar 

  31. J. F. R. Kerr, A. H. Wyllie, and A. R. Cuttie, “Apoptosis, a basic biological phenomenon with wide-ranging implications in tissue kinetics,” Br. J. Cancer 26, 239–245 (1972).

    Article  Google Scholar 

  32. A. H. Wyllie, R. G. Morris, A. L. Smith, and D. Dunlop, “Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis,” J. Pathol. 142, 67–77 (1984).

    Article  Google Scholar 

  33. F. Oberhammer, J. W. Wilson, C. Dive, I. D. Morris, J. A. Hickman, A. E. Wakeling, P. R. Walker, and M. Sikorska, “Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 fragments prior to or in the absence of internucleosomal fragmentation,” EMBO J. 12, 3679–3684 (1993).

    Google Scholar 

  34. C. Diaz and A. J. Schroit, “Role of translocases in the generation of phosphatidylserine asymmetry,” J. Membr. Biol. 151, 1–9 (1996).

    Article  Google Scholar 

  35. B. Verhoven, R. A. Schlegel, and P. Williamson, “Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes,” J. Exp. Med. 182, 1597–1601 (1995).

    Article  Google Scholar 

  36. A. O. Bueverov, O. Yu. Kiseleva, V. T. Ivashkin, N. N. Belushkina, E. Yu. Moskaleva, E. N. Shirokova, and M. V. Maevskaya, “Comparative characteristic of apoptosis of peripheral leukocytes at viral and autoimmune liver diseases,” Ross. Zh. Gastroenterol. Gepatol. Koloproktol. 19 (4), 41–47 (2009).

    Google Scholar 

  37. W. Liles, P. Kiener, and J. Ledbetter, “Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: implications for the regulation of apoptosis in neutrophils,” J. Exp. Med. 184, 429–440 (1996).

    Article  Google Scholar 

  38. I. R. Mackay, N. V. Leskovsek, and N. R. Rose, “Cell damage and autoimmunity: a critical appraisal,” J. Autoimmun. 30, 5–11 (2008).

    Article  Google Scholar 

  39. L. I. Markusheva, M. I. Savina, V. M. Reshina, and R. T. Toguzov, “Chromatin nuclear proteins in evaluating the treatment effectiveness in patients with psoriasis,” Klin. Labor. Diagn., No. 7, 18–20 (2000).

    Google Scholar 

  40. A. V. Zurochka, S. V. Khaidukov, I. V. Kudryavtsev, and V. A. Chereshnev, Flow Cytometry in Medicine and Biology (RIO UrO RAN, Yekaterinburg, 2013), pp. 433–482 [in Russian].

    Google Scholar 

  41. V. N. Ellinidi, N. V. Anikieva, and N. A Maksimova, Practical Immunohistochemistry: Guidelines (VTsERM MChS Rossii, St. Petersburg, 2002) [in Russian].

    Google Scholar 

  42. G. Pearse, “Histopathology of theThymus,” Toxicol Pathol. 34, 515–547 (2006).

    Article  Google Scholar 

  43. S. D. Westerheide, T. L. Kawahara, K. Orton, and R. I. Morimoto, “Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death,” J. Biol. Chem. 281, 9616–9622 (2006).

    Article  Google Scholar 

  44. S. Wickner, M. R. Maurizi, and S. Gottesman, “Posttranslational quality control: folding, refolding, and degrading proteins,” Science 286 (5446), 1888–1893 (1999).

    Article  Google Scholar 

  45. T. M. Melefors, B. Goossen, H. E. Johanson, and M. W. Hentze, “Translational control of 5-aminolevulinate synthase MRNA by iron-responsive elements in erythroid cells,” J. Biol. Chem. 268, 5974–5978 (1993).

    Google Scholar 

  46. D. J. McConkey, B. Zhivotovsky, and S. Orrenius, “Apoptosis - molecular mechanisms and biomedical implications,” Mol. Asp. Med. 17, 1–110 (1996).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences, Yekaterinburg, 620049, Russia

    I. G. Danilova, I. F. Gette, S. Yu. Medvedeva & A. V. Belousova

  2. Ural Federal University, Yekaterinburg, 620002, Russia

    I. G. Danilova, I. F. Gette, S. Yu. Medvedeva, A. V. Belousova, M. O. Tonkushina & A. A. Ostroushko

Authors
  1. I. G. Danilova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. F. Gette
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Yu. Medvedeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. V. Belousova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. O. Tonkushina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. A. Ostroushko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. G. Danilova.

Additional information

Original Russian Text © I.G. Danilova, I.F. Gette, S.Yu. Medvedeva, A.V. Belousova, M.O. Tonkushina, A.A. Ostroushko, 2016, published in Rossiiskie Nanotekhnologii, 2016, Vol. 11, Nos. 9–10.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Danilova, I.G., Gette, I.F., Medvedeva, S.Y. et al. Influence of iron-molybdenum nanocluster polyoxometalates on the apoptosis of blood leukocytes and the level of heat-shock proteins in the cells of thymus and spleen in rats. Nanotechnol Russia 11, 653–662 (2016). https://doi.org/10.1134/S1995078016050049

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1995078016050049

Search

Navigation