Universität Wien, Fakultät für Chemie, Institut für Biophysikalische Chemie, Althanstraße. 14, 1090 Wien, Austria.
Metallomics. 2018 Feb 21;10(2):287-295. doi: 10.1039/c7mt00279c.
Polyoxometalates (POMs) are transition metal complexes that exhibit a broad diversity of structures and properties rendering them promising for biological purposes. POMs are able to inhibit a series of biologically important enzymes, including phosphatases, and thus are able to affect many biochemical processes. In the present study, we analyzed and compared the inhibitory effects of nine different polyoxotungstates (POTs) on two P-type ATPases, Ca-ATPase from skeletal muscle and Na/K-ATPase from basal membrane of skin epithelia. For Ca-ATPase inhibition, an in vitro study was performed and the strongest inhibitors were determined to be the large heteropolytungstate K(CHN)[HSeWO] (SeW) and the Dawson-type POT K[α-PWO] (PW) exhibiting IC values of 0.3 and 0.6 μM, respectively. Promising results were also shown for the Keggin-based POTs KH[CoWTiO] (CoWTi, IC = 4 μM) and Na[α-SiWO] (SiW, IC = 16 μM), K[AsWO(HO)] (AsW, IC = 28 μM) and the lacunary Dawson K[α-HPWO] (PW, IC = 11 μM), whereas low inhibitory potencies were observed for the isopolytungstate Na[HWO] (W, IC = 68 μM) and the Anderson-type Na[TeWO] (TeW, IC = 200 μM). Regarding the inhibition of Na/K-ATPase activity, for the first time an ex vivo study was conducted using the opercular epithelium of killifish in order to investigate the effects of POTs on the epithelial chloride secretion. Interestingly, 1 μM of the most potent Ca-ATPase inhibitor, SeW, showed only a minor inhibitory effect (14% inhibition) on Na/K-ATPase activity, whereas almost total inhibition (99% inhibition) was achieved using PW. The remaining POTs exhibited similar inhibition rates on both ATPases. These results reveal the high potential of some POTs to act as P-type ATPase inhibitors, with SeW showing high selectivity towards Ca-ATPase.
多金属氧酸盐（POMs）是过渡金属配合物，具有广泛的结构和性质多样性，因此在生物领域具有广阔的应用前景。POMs 能够抑制一系列具有重要生物学意义的酶，包括磷酸酶，从而能够影响许多生化过程。在本研究中，我们分析和比较了九种不同的多钨酸盐（POTs）对两种 P 型 ATP 酶，即骨骼肌中的 Ca-ATP 酶和皮肤上皮基底膜中的 Na/K-ATP 酶的抑制作用。对于 Ca-ATP 酶抑制作用，进行了体外研究，并确定最强的抑制剂为大杂多钨酸盐 K(CHN)[HSeWO]（SeW）和 Dawson 型 POT K[α-PWO]（PW），其 IC50 值分别为 0.3 和 0.6 μM。基于 Keggin 的 POTs KH[CoWTiO]（CoWTi，IC = 4 μM）和 Na[α-SiWO]（SiW，IC = 16 μM）、K[AsWO(HO)]（AsW，IC = 28 μM）和空缺 Dawson K[α-HPWO]（PW，IC = 11 μM）也显示出有希望的结果，而同多钨酸盐 Na[HWO]（W，IC = 68 μM）和 Anderson 型 Na[TeWO]（TeW，IC = 200 μM）则表现出较低的抑制潜力。关于 Na/K-ATP 酶活性的抑制，首次使用金鱼的鳃盖上皮进行了离体研究，以研究 POTs 对上皮氯离子分泌的影响。有趣的是，最有效的 Ca-ATP 酶抑制剂 SeW 的 1 μM 浓度仅对 Na/K-ATP 酶活性产生较小的抑制作用（抑制 14%），而 PW 的浓度为 1 μM 时几乎完全抑制（抑制 99%）。其余的 POTs 对两种 ATP 酶表现出相似的抑制率。这些结果表明，一些 POTs 具有作为 P 型 ATP 酶抑制剂的巨大潜力，其中 SeW 对 Ca-ATP 酶具有高选择性。
