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Kerek F, Voicu VA. Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor. Front Endocrinol (Lausanne). 2015;5:233doi: 10.3389/fendo.2014.00233.
Kerek, F., & Voicu, V. A. (2014). Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor. Frontiers in endocrinology, 5233. https://doi.org/10.3389/fendo.2014.00233
Kerek, Franz, and Voicu, Victor A. "Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor." Frontiers in endocrinology vol. 5 (2014): 233. doi: https://doi.org/10.3389/fendo.2014.00233
Kerek F, Voicu VA. Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor. Front Endocrinol (Lausanne). 2015 Jan 23;5:233. doi: 10.3389/fendo.2014.00233. eCollection 2014. PMID: 25667581; PMCID: PMC4304351.
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Front Endocrinol (Lausanne). 2015 Jan 23;5:233. doi: 10.3389/fendo.2014.00233. eCollection 2014.

Spherical Oligo-Silicic Acid SOSA Disclosed as Possible Endogenous Digitalis-Like Factor.

Frontiers in endocrinology

Franz Kerek, Victor A Voicu

Affiliations

  1. SiNatur GmbH , Martinsried , Germany.
  2. Department of Clinical Pharmacology, Toxicology and Psychopharmacology, Carol Davila University of Medicine and Pharmacy , Bucharest , Romania.

PMID: 25667581 PMCID: PMC4304351 DOI: 10.3389/fendo.2014.00233

Abstract

The Na(+)/K(+)-ATPase is a membrane ion-transporter protein, specifically inhibited by digitalis glycosides used in cardiac therapy. The existence in mammals of some endogenous digitalis-like factors (EDLFs) as presumed ATPase ligands is generally accepted. But the chemical structure of these factors remained elusive because no weighable amounts of pure EDLFs have been isolated. Recent high-resolution crystal structure data of Na(+)/K(+)-ATPase have located the hydrophobic binding pocket of the steroid glycoside ouabain. It remained uncertain if the EDLF are targeting this steroid-receptor or another specific binding site(s). Our recently disclosed spherical oligo-silicic acids (SOSA) fulfill the main criteria to be identified with the presumed EDL factors. SOSA was found as a very potent inhibitor of the Na(+)/K(+)-ATPase, Ca(2+)-ATPase, H(+)/K(+)-ATPase, and of K-dp-ATPase, with IC50 values between 0.2 and 0.5 μg/mL. These findings are even more astonishing while so far, neither monosilicic acid nor its poly-condensed forms have been remarked biologically active. With the diameter ϕ between 1 and 3 nm, SOSA still belong to molecular species definitely smaller than silica nano-particles with ϕ > 5 nm. In SOSA molecules, almost all Si-OH bonds are displayed on the external shell, which facilitates the binding to hydrophilic ATPase domains. SOSA is stable for long term in solution but is sensitive to freeze-drying, which could explain the failure of countless attempts to isolate pure EDLF. There is a strong resemblance between SOSA and vanadates, the previously known general inhibitors of P-type ATPases. SOSA may be generated endogenously by spherical oligomerization of the ubiquitously present monosilicic acid in animal fluids. The structure of SOSA is sensitive to the concentration of Na(+), K(+), Ca(2+), Mg(2+), and other ions suggesting a presumably archaic mechanism for the regulation of the ATPase pumps.

Keywords: ATPase regulation; digitalis-like factor; oligo silicic-acid; ouabain

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