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Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems.
- Source :
-
Journal of Enzyme Inhibition & Medicinal Chemistry . Dec2019, Vol. 34 Issue 1, p500-509. 10p. - Publication Year :
- 2019
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14756366
- Volume :
- 34
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Enzyme Inhibition & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 140468391
- Full Text :
- https://doi.org/10.1080/14756366.2018.1557653