Inhibition kinetics of brain butyrylcholinesterase by Cd2+ and Zn2+, Ca2+ or Mg2+ reactivates the inhibited enzyme

Çokuğraş, A. Neşe; Tezcan, E. Ferhan

doi:10.1016/0020-711x(93)90589-7

Cited by 18 publications

(3 citation statements)

References 14 publications

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“…DOG is a diacyl glycerol analog of the classical stimulator of calcium-dependent PKC-α signaling. Previously, the interaction between ChE and PKC-α is shown [7,[8][9][10][11][12][13][14]. In this study, we stimulated embryonic cell line R28 with DOG under normal cell conditions as well as knocking BChE down.…”

Section: Resultsmentioning

confidence: 89%

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PKC stimulation increases expression of Cholinesterases in R28 cell line

Bodur¹,

Layer²

2014

Turk J Bioch

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Objective: Previously we have shown a counter-regulation between cholinesterases (ChEs) through both anti-sense Butyrylcholinesterase (BChE) transfection and knock-down by siRNAs in R28 cells. In course of this counter-regulation, the status of the cell growth-and differentiation-related signaling pathways PKC and ERK were also changed. Down-regulation of BChE led to an increased PKC-α expression. Here, we demonstrate that this interaction between ChEs and PKC is reciprocal. Methods: R28 cells were treated with final 10 µM Di-octanoyl glycerol (DOG) and 10 nM siRNAs against BChE. Expression analysis was done by RT-PCR, Western Blot, IHC and activity assays. Results: DOG treatment along with BChE knockdown resulted in increased PKC-α expression, as compared with DOG treatment alone. Change in ERK1 expression was not as profound. In R28 cells, DOG stimulation led to marked rapid increase in both AChE and BChE expression. Conclusion: PKC stimulation during BChE knockdown caused functional, saturated AChE expression. Increased PKC-α expression suggests that PKC-α is not only regulated by its stimulators but also by the absence of BChE. While ChEs are counter-regulated, activation of PKC has both reciprocal and additive outcome through cholinergic pathway. Thus, effects of DOG stimulation expose yet another interaction between calcium dependent PKC-α and ChEs showing that any measure of disclosure on neurodegenerative diseases must not only consider cholinergic control but also monitor the PKC pathway.

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Section: Resultsmentioning

confidence: 89%

“…ChEs also regulate voltage-dependent Ca 2+ currents and neurite growth [11,12]. In addition, Ca 2+ reactivates inhibited BChE, signifying an important link between Ca 2+ and functionally active ChE proteins [13].…”

Section: Introductionmentioning

confidence: 99%

PKC stimulation increases expression of Cholinesterases in R28 cell line

Bodur¹,

Layer²

2014

Turk J Bioch

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“…According to the literature, there is no sound data to compare these kinetic values particularly for k m or k s , and k cat or V max regarding human serum BuChE. Tezcan and co-workers reported k s values for purified human serum BuChE, human serum BuChE and sheep brain BuChE as 0.128 ± 0.012 mM, 0.11 mM and 0.14 mM, respectively [34–36]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of Butyrylcholinesterase with Fluorobenzylcymserine, An Experimental Alzheimer's Drug Candidate: Validation of Enzoinformatics Results by Classical and Innovative Enzyme Kinetic Analyses

Kamal

Shakil

Nawaz

et al. 2017

CNSNDDT

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Background Selective butyrylcholinesterase (BuChE)-inhibition, increases acetylcholine (ACh) levels. In rodents, this inhibition is known to boost cognition. Also, this occurs without the typical unwanted adverse effects of acetylcholinesterase-inhibitors or AChE-Is. The novel compound, fluorobenzylcymserine (FBC), is derived from our effort to design a selective BuChE-inhibitor. Also, we wanted to check whether butyrylcholinesterase-inhibitors (BuChE-Is) possessed an edge over AChE-Is in Alzheimer’s disease (AD) in terms of efficacy and/or tolerance. Method FBC was synthesized as reported earlier while enzymatic activity of BuChE was calculated by Ellman-technique. Molecular docking was performed using Autodock4.2. We applied classical as well as innovative analyses of enzyme-kinetics for exploring “FBC:human BuChE-interaction”. The mode of inhibition and kinetic parameters were also determined. Results Docking results displayed two strong interacting sites for FBC. One of these binding sites was previously identified as a deep narrow groove having polar aromatic residues while a second site was identified during this study which displayed better interaction and was lined with aliphatic and sulphur containing residues. At low concentrations of BuChE, the IC50 was found to be very low i.e. 4.79 and 6.10 nM for 12 and 36 μg, respectively, whereas it increased exponentially by increasing the units of BuChE. Conclusion These analyses indicate that FBC is an interesting AD drug candidate that could provide a potent and partial mixed type of inhibition of human BuChE.

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