ISE, University of Algarve, 8005-139 Faro, Portugal; CCMar, University of Algarve, 8005-139 Faro, Portugal.
CCMar, University of Algarve, 8005-139 Faro, Portugal.
J Inorg Biochem. 2019 Aug;197:110700. doi: 10.1016/j.jinorgbio.2019.110700. Epub 2019 Apr 29.
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 [PWO], 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 CsHPVO (PV) and we confront the data with activity of other commonly encountered polyoxovanadates, decavanadate (V) and monovanadate (V). The X-ray crystal structure of PV was solved and contains two trans-bicapped α-Keggin anions HPVO. The anion is built up from the classical Keggin structure [(PO)@(VO)] capped by two [VO] units. PV (10 μM) exhibited higher ex-vivo inhibitory effect on Na/K-ATPase (78%) than was observed at the same concentrations of V (66%) or V (33%). Moreover, PV is also a potent in vitro inhibitor of the Ca-ATPase activity (IC 5 μM) exhibiting stronger inhibition than the previously reported activities for V (15 μM) and V (80 μM). Putting it all together, when compared both P-typye ATPases it is suggested that PV exibited a high potential to act as an in vivo inhibitor of the Na/K-ATPase associated with chloride secretion.
多金属氧酸盐（POMs）是一类有前途的无机 P 型 ATP 酶抑制剂。用于研究 POMs 对这些 ATP 酶影响的实验模型通常是使用来自几种膜源的囊泡的体外模型。最近，一些多钨酸盐，如 Dawson 阴离子[PWO]，被证明是有效的 P 型 ATP 酶抑制剂；在体外和体内都具有活性。在本研究中，我们将高度活跃的上皮皮肤基底膜 Na/K-ATP 酶抑制剂的范围从基础膜拓宽到双帽 Keggin 型阴离子磷十四钒酸盐 CsHPVO（PV），并将数据与其他常见的多钒酸盐、十钒酸盐（V）和一钒酸盐（V）的活性进行对比。PV 的 X 射线晶体结构已被解决，其中包含两个反式双帽 α-Keggin 阴离子 HPVO。该阴离子由经典的 Keggin 结构[(PO)@(VO)]构成，由两个[VO]单元封端。PV（10 μM）在离体条件下对 Na/K-ATP 酶的抑制作用（78%）高于相同浓度下的 V（66%）或 V（33%）。此外，PV 也是一种有效的 Ca-ATPase 活性的体外抑制剂（IC 5 μM），其抑制作用强于先前报道的 V（15 μM）和 V（80 μM）的活性。综上所述，当与两种 P 型 ATP 酶进行比较时，建议 PV 具有作为与氯分泌相关的 Na/K-ATP 酶体内抑制剂的高潜力。
