Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems
Copyright policy )Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems
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.
Magnetic Resonance Spectroscopy, Synaptosomal-Associated Protein 25, Cell Survival, RM1-950, Calorimetry, tellimagrandin i, Exocytosis, Inhibitory Concentration 50, Mice, Structure-Activity Relationship, Protein Phosphatase 1, synaptosomal exocytosis, Animals, Humans, Elméleti orvostudományok, protein phosphatase-2a, Protein Phosphatase 2, Enzyme Inhibitors, Phosphorylation, Muscle, Skeletal, Cerebral Cortex, mahtabin a, protein phosphatase-1, Orvostudományok, Surface Plasmon Resonance, Hydrolyzable Tannins, Therapeutics. Pharmacology, Research Paper, HeLa Cells, Synaptosomes
Magnetic Resonance Spectroscopy, Synaptosomal-Associated Protein 25, Cell Survival, RM1-950, Calorimetry, tellimagrandin i, Exocytosis, Inhibitory Concentration 50, Mice, Structure-Activity Relationship, Protein Phosphatase 1, synaptosomal exocytosis, Animals, Humans, Elméleti orvostudományok, protein phosphatase-2a, Protein Phosphatase 2, Enzyme Inhibitors, Phosphorylation, Muscle, Skeletal, Cerebral Cortex, mahtabin a, protein phosphatase-1, Orvostudományok, Surface Plasmon Resonance, Hydrolyzable Tannins, Therapeutics. Pharmacology, Research Paper, HeLa Cells, Synaptosomes
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