scholarly journals Beryllium competitively inhibits brain myo-inositol monophosphatase, but unlike lithium does not enhance agonist-induced inositol phosphate accumulation

1993 ◽  
Vol 291 (2) ◽  
pp. 369-374 ◽  
Author(s):  
W S Faraci ◽  
S H Zorn ◽  
A V Bakker ◽  
E Jackson ◽  
K Pratt
Keyword(s):  
Rat Brain ◽  
Inositol Phosphate ◽  
Bipolar Depression ◽  
Neuroblastoma Cell ◽  
Brain Slices ◽  
Human Neuroblastoma Cell ◽  
Inositol Monophosphatase ◽  
Human Neuroblastoma ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation

Despite limiting side-effects, lithium is the drug of choice for the treatment of bipolar depression. Its action may be due, in part, to its ability to dampen phosphatidylinositol turnover by inhibiting myo-inositol monophosphatase. Beryllium has been identified as a potent inhibitor of partially purified myo-inositol monophosphatase isolated from rat brain (Ki = 150 nM), bovine brain (Ki = 35 nM), and from the human neuroblastoma cell line SK-N-SH (Ki = 85 nM). It is over three orders of magnitude more potent than LiCl (Ki = 0.5-1.2 mM). Kinetic analysis reveals that beryllium is a competitive inhibitor of myo-inositol monophosphatase, in contrast with lithium which is an uncompetitive inhibitor. Inhibition of exogenous [3H]inositol phosphate hydrolysis by beryllium (IC50 = 250-300 nM) was observed to the same maximal extent as that seen with lithium in permeabilized SK-N-SH cells, reflecting inhibition of cellular myo-inositol monophosphatase. However, in contrast with that observed with lithium, agonist-induced accumulation of inositol phosphate was not observed with beryllium in permeabilized and non-permeabilized SK-N-SH cells and in rat brain slices. Similar results were obtained in permeabilized SK-N-SH cells when GTP-gamma-S was used as an alternative stimulator of inositol phosphate accumulation. The disparity in the actions of beryllium and lithium suggest that either (1) selective inhibition of myo-inositol monophosphatase does not completely explain the action of lithium on the phosphatidylinositol cycle, or (2) that uncompetitive inhibition of myo-inositol monophosphatase is a necessary requirement to observe functional lithium mimetic activity.

A Method to Measure Simultaneously Cyclic AMP and Inositol Phosphate Accumulation in Rat Brain Slices

1991 ◽  
Vol 56 (4) ◽  
pp. 1114-1120 ◽  
Author(s):  
D. Morin ◽  
R. Zini ◽  
V. Querol-Ferrer ◽  
R. Sapena ◽  
J. P. Tillement
Keyword(s):  
Cyclic Amp ◽  
Rat Brain ◽  
Inositol Phosphate ◽  
Brain Slices ◽  
Phosphate Accumulation ◽  
Inositol Phosphate Accumulation

scholarly journals ANALYSIS OF THE ANTIOXIDANT ACTIVITY OF GERANIOL EMPLOYING VARIOUS IN-VITRO MODELS: RELEVANCE TO NEURODEGENERATION IN DIABETIC NEUROPATHY

2017 ◽  
Vol 10 (7) ◽  
pp. 101 ◽  
Author(s):  
Sathya N Prasad ◽  
Murali Muralidhara
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Activity ◽  
Rat Brain ◽  
Neuroblastoma Cell ◽  
Brain Regions ◽  
In Vitro Models ◽  
Human Neuroblastoma Cell ◽  
Pathological Feature ◽  
Human Neuroblastoma

Objective: The aim of this study was to analyze antioxidant effect of geraniol (GE) in different in vitro models.Methods: Initially, the antioxidant activity of GE was assessed by diphenyl picrylhydrazyl radical (DPPH) assay. The modulatory effect of GE against 2,2’-azobis(2-amidinopropane) dihydrochloride induced lipid peroxidation in rat brain regions (cortex and cerebellum) and sciatic nerve (SN) homogenates was determined. Further, the effect of GE was assessed against hyperglycemia-induced oxidative stress (OS) in SHSY5Y, a human neuroblastoma cell line.Results: GE proved to be a good scavenger of DPPH free radical (inhibitory concentration 50% [IC50] value = 663 nmol) and could lower the lipid peroxidation levels in rat brain tissue and SN homogenates (25-40%). Further, it rescue the SHSY5Y cells from hyperglycemia-induced death. Co-exposure of GE with the IC50 level of glucose (100 mM) lowered the levels of reactive oxygen species, hydrogen peroxides and 3-nitrotyrosine levels with concomitant elevation in the glutathione levels (about two folds).Conclusion: Collectively from these findings and other studies previously conducted (from our lab and others) emphasize the potential benefit of GE against OS, a progressive pathological feature of neurodegenerative disorders. 

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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