Effects of Water-Soluble Polysubstituted Fullerene Derivatives on Sarcoplasmic Reticulum Ca2+-ATPase and Cyclic Guanosine Monophosphate Phosphodiesterase Activities
| Autor: | Pavel A. Troshin, Ekaterina A. Khakina, R. A. Kotel’nikova, L. V. Tat’yanenko, I. Yu. Pikhteleva, A. B. Kornev, Alexander I. Kotelnikov, O. V. Dobrokhotova, D. A. Poletaeva |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Pharmaceutical Chemistry Journal. 47:405-408 |
| ISSN: | 1573-9031 0091-150X |
| DOI: | 10.1007/s11094-013-0969-3 |
| Popis: | 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
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