a Department of Medical Chemistry, Faculty of Medicine , University of Debrecen , Debrecen , Hungary.
b MTA-DE Cell Biology and Signalling Research Group, Faculty of Medicine , University of Debrecen , Debrecen , Hungary.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):500-509. doi: 10.1080/14756366.2018.1557653.
Several ellagitannins inhibited the activity of protein phosphatase-1 (PP1) and -2 A (PP2A) catalytic subunits (PP1c and PP2Ac) with preferential suppression of PP1c over PP2Ac. The inhibitory potency for PP1c followed the order of tellimagrandin I > mahtabin A > praecoxin B > 1.2-Di-O-galloyl-4.6-(S)-HHDP-β-D-glucopyranose > pedunculagin with IC values ranging from 0.20 µM to 2.47 µM. The interaction of PP1c and tellimagrandin I was assessed by NMR saturation transfer difference, surface plasmon resonance, isothermal titration calorimetry, and microscale thermophoresis based binding techniques. Tellimagrandin I suppressed viability and phosphatase activity of HeLa cells, while mahtabin A was without effect. Conversely, mahtabin A increased the phosphorylation level of SNAP-25 and suppressed exocytosis of cortical synaptosomes, whereas tellimagrandin I was without influence. Our results establish ellagitannins as partially selective inhibitors of PP1 and indicate that these polyphenols may act distinctly in cellular systems depending on their membrane permeability and/or their actions on cell membranes.
几种鞣花单宁抑制蛋白磷酸酶-1（PP1）和-2A（PP2A）催化亚基（PP1c 和 PP2Ac）的活性，对 PP1c 的抑制作用优先于 PP2Ac。对 PP1c 的抑制活性顺序为 Tellimagrandin I > Mahtabin A > Praecoxin B > 1,2-二-O-没食子酰基-4,6-（S）-HHDP-β-D-吡喃葡萄糖 > 鞣花丹宁，IC 值范围为 0.20 µM 至 2.47 µM。通过 NMR 饱和转移差、表面等离子体共振、等温滴定量热法和基于微尺度热泳的结合技术评估了 PP1c 和 Tellimagrandin I 的相互作用。Tellimagrandin I 抑制了 HeLa 细胞的活力和磷酸酶活性，而 Mahtabin A 则没有效果。相反，Mahtabin A 增加了 SNAP-25 的磷酸化水平，并抑制了皮质突触小体的胞吐作用，而 Tellimagrandin I 则没有影响。我们的研究结果确立了鞣花单宁是 PP1 的部分选择性抑制剂，并表明这些多酚类物质可能根据其膜通透性和/或对细胞膜的作用在细胞系统中表现出不同的作用。
