Effects of water-soluble polysubstituted fullerene derivatives on sarcoplasmic reticulum Ca2+-ATPase and cyclic guanosine monophosphate phosphodiesterase activities

L. V. Tat'Yanenko, R. A. Kotel'Nikova, D. A. Poletaeva, O. V. Dobrokhotova, I. Yu Pikhteleva, A. B. Kornev, E. A. Khakina, P. A. Troshin, A. I. Kotel'Nikov

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The effects of new fullerene derivatives on the functioning of the hydrolases sarcoplasmic reticulum (SR) Ca2+-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) were studied. Most of the fullerene derivatives studied were found to inhibit the activity of both enzymes. Thus, compounds PSF-1, PSF-II, and PSF-III completely inhibited Ca 2+ transport at a concentration of 0.009 mM but inhibited ATP hydrolysis by only 55 ± 6%, 42 ± 8%, and 60 ± 6% respectively, thus uncoupling the hydrolytic and transport functions of the enzyme. This induced changes in the extra- and intracellular Ca2+ ion levels and affected adhesion of metastatic cells to the capillary endothelium. Compound PSF-III had noncompetitive, reversible effects on the hydrolytic function of SR Ca2+-ATPase with K i = 1.6 × 10 -6 M. All the fullerene derivatives studied inhibited cGMP PDE function and could induce an antiaggregation effect which resulted from accumulation of the cGMP PDE substrate, i.e., cGMP, which is a second messenger in living organisms. These results can be used to predict the potential therapeutic effects of the fullerene derivatives studied.

Original languageEnglish
Pages (from-to)405-408
Number of pages4
JournalPharmaceutical Chemistry Journal
Volume47
Issue number8
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • cyclic guanosine monophosphate phosphodiesterase
  • polysubstituted fullerene derivatives
  • Sarcoplasmic reticulum Ca-Mg-ATPase

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