Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems

Journal of Enzyme Inhibition and Medicinal Chemistry

Beáta Lontay¹  Bálint Bécsi¹  Dániel Horváth¹  Andrea Kiss¹  Zoltán Kónya²  Ferenc Erdődi²  Mária Raics³  Katalin E. Kövér³ 

[1] Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;MTA-DE Cell Biology and Signalling Research Group, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;Institute of Chemistry, University of Debrecen, Debrecen, Hungar;

关键词: Tellimagrandin I;    mahtabin A;    protein phosphatase-1;    protein phosphatase-2A;    synaptosomal exocytosis;   

DOI  :  10.1080/14756366.2018.1557653

来源: publisher

【 摘 要 】

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 IC50 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-25Thr138 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.

【 授权许可】

CC BY