Inhibition of Na⁺/K⁺ - and Ca²⁺ -ATPase activities by phosphotetradecavanadate

Autor(en)

Gil Fraqueza, Juan Fuentes, Lukáš Krivosudský, Saikat Dutta, Sib Sankar Mal, Alexander Roller, Gerald Giester, Annette Rompel, Manuel Aureliano

Abstrakt

Polyoxometalates (POMs) are promising inorganic inhibitors for P-type ATPases. The experimental models used to study the effects of POMs on these ATPases are usually in vitro models using vesicles from several membrane sources. Very recently, some polyoxotungstates, such as the Dawson anion [P2W18O62](6-), were shown to be potent P-type ATPase inhibitors; being active in vitro as well as in ex-vivo. In the present study we broaden the spectrum of highly active inhibitors of Na+/K+-ATPase from basal membrane of epithelial skin to the bi-capped Keggin-type anion phosphotetradecavanadate Cs(5.6)H(3)APV(14)O(42) (PV14) and we confront the data with activity of other commonly encountered polyoxovanadates, decavanadate (V10) and monovanadate (V-1). The X-ray crystal structure of PV14 was solved and contains two trans-bicapped alpha-Keggin anions HxPV14O42(9-x)-. The anion is built up from the classical Keggin structure [(PO4)@(V12O36)] capped by two [VO] units. PV14 (10 M) exhibited higher ex-vivo inhibitory effect on Na+/K+-ATPase (78%) than was observed at the same concentrations of V-10 (66%) or V-1 (33%). Moreover, PV14 is also a potent in vitro inhibitor of the Ca2+-ATPase activity (IC50 5 mu M) exhibiting stronger inhibition than the previously reported activities for V-10 (15 mu M) and V-1 (80 mu M). Putting it all together, when compared both P-typye ATPases it is suggested that PV14 exibited a high potential to act as an in vivo inhibitor of the Na+/K+-ATPase associated with chloride secretion.

Organisation(en)

Core Facility für Kristallstrukturanalyse, Institut für Anorganische Chemie, Institut für Mineralogie und Kristallographie, Institut für Biophysikalische Chemie

Externe Organisation(en)

Universidade do Algarve, Univerzita Komenského v Bratislave, National Institute of Technology Karnataka, Universität Wien

Journal

Journal of Inorganic Biochemistry

Band

197

Anzahl der Seiten

7

ISSN

0162-0134

DOI

https://doi.org/10.1016/j.jinorgbio.2019.110700

Publikationsdatum

04-2019

Peer-reviewed

Ja

ÖFOS 2012

104003 Anorganische Chemie, 104004 Chemische Biologie, 105113 Kristallographie, 104024 Röntgenstrukturanalyse

Schlagwörter

ASJC Scopus Sachgebiete

Biochemistry, Inorganic Chemistry

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/0d97b7c5-e299-42be-9400-27d790aa9a0b