Papers by Davit Mikeladze
Synaptic Constituents in Health and Disease, 1980
Publisher Summary This chapter presents a study of synthesis of acetylphosphocholine in the brain... more Publisher Summary This chapter presents a study of synthesis of acetylphosphocholine in the brain. In brain tissue, a compound was found, which by its electrophoretic and Chromatographic mobility differs from all the other known derivates of choline. The compound has a similar activity to that of acetylcholine. It contains the phosphoryl and acetyl groups, and choline too. After incubation of homogenate or synaptic membrane proteins with 14C-aceticacid, 3H-choline, and 32P-ATP, all the three radioactive labels are localized in this compound. Quantitative analysis of the compound leads to the conclusion that it is acetylphosphocholine, where acetyl group and choline are bound to the phosphoryl moiety. The biosynthesis of acetylphosphocholine was studied. This compound was shown to be formed from acetylphosphate and choline, but not from acetyl CoA and phosphocholine. It was elucidated that acetylphosphocholine might be formed also, from CDP-choline. For this reaction only acetic acid and ATP, but not acetyl CoA are necessary.
AIMS Neuroscience, 2020
Mislocalization and abnormal expression of N-methyl-D-aspartate glutamate receptor (NMDAR) subuni... more Mislocalization and abnormal expression of N-methyl-D-aspartate glutamate receptor (NMDAR) subunits is observed in several brain disorders and pathological conditions. Recently, we have shown that intraperitoneal injection of the gut neurotoxin p-cresol induces autism-like behavior and accelerates seizure reactions in healthy and epilepsy-prone rats, respectively. In this study, we evaluated the expression of GLUN2B and GLUN2A NMDAR subunits, and assessed the activity of cAMP-response element binding protein (CREB) and Rac1 in the hippocampi and nucleus accumbens of healthy and epilepsy-prone rats following p-cresol administration. We have found that subchronic intraperitoneal injection of p-cresol induced differential expression of GLUN2B and GLUN2A between the two brain regions, and altered the GLUN2B/GLUN2A ratio, in rats in both groups. Moreover, p-cresol impaired CREB phosphorylation in both brain structures and stimulated Rac activity in the hippocampus. These data indicate that p-cresol differently modulates the expression of NMDAR subunits in the nucleus accumbens and hippocampi of healthy and epilepsyprone rats. We propose that these differences are due to the specificity of interactions between dopaminergic and glutamatergic pathways in these structures.
Ukrainskiĭ biokhimicheskiĭ zhurnal
The suggested sequence of the reactions differs from those presented in literature and includes t... more The suggested sequence of the reactions differs from those presented in literature and includes the following compounds as intermediate ones: the complex of enzyme having 2ATP and two residues of phosphoric acid; the complex of enzyme having four residues of phosphoric acid; the complex of enzyme containing two residues of phosphoric acid and two residues of succinic acid. Sequences of the reactions suggested in literature involve as intermediate compounds a phosphorylated derivative of the enzyme (E--P), phosphorylated derivative CoA linked with the enzyme (E.CoA--P), a high-ergic compound of the enzyme with CoA (E.CoA) and succinyl phosphate linked with the enzyme (E.succinyl--P).
Georgian medical news, 2006
Value of mannose-binding proteins was determined in plasma of pregnant women with no complication... more Value of mannose-binding proteins was determined in plasma of pregnant women with no complications and also in pregnant women with some infections using affinitive chromatography. It was found that the concentration of mannose-binding proteins in blood plasma of women equals 0.152+/-0.025 mg/ml. The concentration of mannose-binding proteins in blood plasma increase during the consecutive trimesters of noncomplicated pregnancy. In the first trimester it equals 0.198+/-0.032 mg/ml, in the second 0.257+/-0.027 mg/ml and in the third trimester 0.345+/-0.034 mg/ml. We also found that the concentration of mannose-binding proteins in blood plasma of pregnant woman suffering with chlamydial infection equals 1.025+/-0.115 mg/ml, and in blood plasma of pregnant woman suffering with cytomegalovirus infection 1.278+/-0.144 mg/ml. The obtained data confirm a hypothesis of increased activity of innate immune system during pregnancy. Also according to this results complications accompanied by chla...
Akusherstvo i ginekologii͡a, 1988
Biokhimii͡a (Moscow, Russia), 1979
Isoelectric focusing of a purified fraction of thermostable modulator of 3',5'-AMP-depend... more Isoelectric focusing of a purified fraction of thermostable modulator of 3',5'-AMP-dependent protein kinase revealed five individual proteins, the main protein having an isoelectric point of 4,05. The molecular weight of this protein as determined by gel filtration is 8000--9000. The protein with a pI of 4,05 binds Ca2+ and in contrast to the original modulator inhibits the endogenous 3',5'-AMP-dependent phosphorylation of synaptic membranes. An addition of the original modulator fraction to the microsomes isolated from nervous tissue increases the Mg, Ca-ATPase activity and absorption of 45Ca. Neither the protein with a pI of 4,05 nor other individual proteins affect the activity of transport ATPase. The activating effect is partly restored after mixing of all the five subfractions. It is assumed that these proteins are aggregated by Ca2+ and change the activity of ATPase or membrane 3',5'-AMP-dependent protein kinase depending on the concentration of calciu...
Neurochemical Research, 2001
The effects of the lectins concanavalin A, WGA, ricin, abrin, and the mistletoe lectins from Visc... more The effects of the lectins concanavalin A, WGA, ricin, abrin, and the mistletoe lectins from Viscum album MLI, MLII, and MLIII on the binding of ligands of the NMDA and sigma receptors in rat hippocampus synaptic plasma membranes were investigated. Binding of [ 3 H]MK-801, [ 3 H]glutamate, [ 3 H]5,7-DCKA, and [ 3 H]glycine to the membranes was decreased by 40-60% after addition of galactose-specific lectins (mistletoe lectins MLI, MLII, ricin, abrin) at concentrations of 0.01 mg/ml, but was not affected by the glucose-and mannose-specific lectin Con A, an acetylglucosamine-specific lectin WGA, or an acetylgalactosamine-specific lectin MLIII. The binding of [ 3 H]SKF 10047 was decreased only in the presence of MLIII and did not change after addition of the other lectins. It is suggested that lectin-sensitive ligand binding sites of sigma-and NMDA receptors are located separately, and that the carbohydrate side chains of the sigma receptor do not participate in the modulation of the NMDA-receptor.
Journal of Biological Physics and Chemistry, 2010
ABSTRACT Many occupational studies have inferred central nervous system dysfunction as an outcome... more ABSTRACT Many occupational studies have inferred central nervous system dysfunction as an outcome of toluene exposure. The sleep–wakefulness cycle is a universal model of brain integrative activity, which reflects multiple levels of the homeostatic processes. In this study, the structure of the sleep–wakefulness cycle of the rat, the quantitative ratio of phases, their electrographic characteristics and changes in the content of intraventricular glutamate, aspartate and arginine were determined in the normal state, after 10 days inhalation of toluene, 5 days after its withdrawal and after the action of chlorogenic acid, one of the most abundant polyphenols in the human diet with antioxidant, anticarcinogenic and neuroprotective properties. Using electroencephalography for the determination of behavioural state we found that toluene inhalation disrupts the normal sleep cycle, increased the total length of wakefulness, suppressed REM sleep, and reduced non-REM sleep. We have furthermore shown that the content of intraventricular glutamate was increased in all states of the sleep–wakefulness cycle while the concentration of aspartate was decreased. Arginine was diminished during wakefulness and non-REM sleep and increased in REM sleep. Intraperitoneal administration of chlorogenic acid resulted in rapid normalization both of the duration of the sleep–wakefulness cycle and the amino acid contents. These findings suggest that toluene engenders disturbance of excitatory amino acid and nitric oxide metabolism, which is reflected in the dynamics of the sleep–wakefulness cycle and duration of its phases.
…, 2009
... Eka Kvaratskhelia a Ekaterine Maisuradze a Nino G. Dabrundashvili a ... Considering that lymp... more ... Eka Kvaratskhelia a Ekaterine Maisuradze a Nino G. Dabrundashvili a ... Considering that lympho-cyte glutamate receptor activation by NMDA increases the levels of intracellular calcium andROS [4] and that oxidative stress is a ubiquitous inducer of IL-8 gene ex-pression, it ...
PubMed, Jun 21, 2018
Saccharomyces cerevisiae can utilize a wide range of carbon sources; however, in the presence of ... more Saccharomyces cerevisiae can utilize a wide range of carbon sources; however, in the presence of glucose the use of alternate carbon sources would be repressed. Several genes involved in the metabolic pathways exert these effects. Among them, the zinc finger protein, Mig1 (multicopy inhibitor of GAL gene expression) plays important roles in glucose repression of Saccharomyces cerevisiae. To investigate whether the alleviation of glucose effect would result in a switch to oxidative production pathway, MIG1 were disrupted in a haploid laboratory strain (2805) of S. cerevisiae. The impact of this disruption was studied under fully aerobic conditions when glucose was the sole carbon source. Our results showed that glucose repression was partly alleviated; i.e., ethanol, as a significant fermentation marker, and acetate productions were respectively decreased by 14.13% and 43.71% compared to the wild type. In ΔMIG1 strain, the metabolic shifting on the aerobic pathway and a significant increase in pyruvate and glycerol production suggested it as an optimally productive industrial yeast strain. However, further studies are needed to confirm these findings.
PubMed, Aug 6, 2019
Background: Although Saccharomyces cerevisiae has several industrial applications, there are stil... more Background: Although Saccharomyces cerevisiae has several industrial applications, there are still fundamental problems associated with sequential use of carbon sources. As such, glucose repression effect can direct metabolism of yeast to preferably anaerobic conditions. This leads to higher ethanol production and less efficient production of recombinant products. The general glucose repression system is constituted by MIG1, TUP1 and SSN6 factors. The role of MIG1 is known in glucose repression but the evaluation of effects on aerobic/anaerobic metabolism by deletion of MIG1 and constructing an optimal strain brand remains unclear and an objective to be explored. Methods: To find the impact of MIG1 in induction of glucose-repression, the Mig1 disruptant strain (ΔMIG1) was produced for comparing with its congenic wild-type strain (2805). The analysis approached for changes in the rate of glucose consumption, biomass yield, cell protein contents, ethanol and intermediate metabolites production. The MIG1 disruptant strain exhibited 25% glucose utilization, 12% biomass growth rate and 22% protein content over the wild type. The shift to respiratory pathway has been demonstrated by 122.86 and 40% increase of glycerol and pyruvate production, respectively as oxidative metabolites, while the reduction of fermentative metabolites such as acetate 35.48 and ethanol 24%. Results: Results suggest that ΔMIG1 compared to the wild-type strain can significantly present less effects of glucose repression. Conclusion: The constructed strain has more efficient growth in aerobic cultivations and it can be a potential host for biotechnological recombinant yields and industrial interests.
PubMed, Apr 1, 2023
Objective: Thyroid hormones are involved in the pathogenesis of various neurological disorders. I... more Objective: Thyroid hormones are involved in the pathogenesis of various neurological disorders. Ischemia/hypoxia that induces rigidity of the actin filaments, which initiates neurodegeneration and reduces synaptic plasticity. We hypothesized that thyroid hormones via alpha-v-beta-3 (αvβ3) integrin could regulate the actin filament rearrangement during hypoxia and increase neuronal cell viability. Materials and methods: In this experimental study, we analysed the dynamics of actin cytoskeleton according to the G/F actin ratio, cofilin-1/p-cofilin-1 ratio, and p-Fyn/Fyn ratio in differentiated PC-12 cells with/without T3 hormone (3,5,3'-triiodo-L-thyronine) treatment and blocking αvβ3-integrin-antibody under hypoxic conditions using electrophoresis and western blotting methods. We assessed NADPH oxidase activity under the hypoxic condition by the luminometric method and Rac1 activity using the ELISA-based (G-LISA) activation assay kit. Results: The T3 hormone induces the αvβ3 integrin-dependent dephosphorylation of the Fyn kinase (P=0.0010), modulates the G/F actin ratio (P=0.0010) and activates the Rac1/NADPH oxidase/cofilin-1 (P=0.0069, P=0.0010, P=0.0045) pathway. T3 increases PC-12 cell viability (P=0.0050) during hypoxia via αvβ3 integrin-dependent downstream regulation systems. Conclusion: The T3 thyroid hormone may modulate the G/F actin ratio via the Rac1 GTPase/NADPH oxidase/ cofilin1signaling pathway and αvβ3-integrin-dependent suppression of Fyn kinase phosphorylation.
Current Molecular Medicine, Mar 1, 2021
Background: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintai... more Background: Elevation of plasma free fatty acids as a principal aspect of type 2 diabetes maintains etiologically insulin insensitivity in target cells. TNF-α inhibitory effects on key insulin signaling pathway elements remain to be verified in insulinresistant hepatic cells. Thus, TNF-α knockdown effects on the key elements of insulin signaling were investigated in the palmitate-induced insulin-resistant hepatocytes. The Akt serine kinase, a key protein of the insulin signaling pathway, phosphorylation was monitored to understand the TNF-α effect on probable enhancing of insulin resistance. Methods: Insulin-resistant HepG2 cells were produced using 0.5 mM palmitate treatment and shRNA-mediated TNF-α gene knockdown and its down-regulation confirmed using ELISA technique. Western blotting analysis was used to assess the Akt protein phosphorylation status. Results: Palmitate-induced insulin resistance caused TNF-α protein overexpression 1.2-, 2.78, and 2.25- fold as compared to the control cells at post-treatment times of 8 h, 16 h, and 24 h, respectively. In the presence of palmitate, TNF-α expression showed around 30% reduction in TNF-α knockdown cells as compared to normal cells. In the TNF-α down-regulated cell, Akt phosphorylation was approximately 62% more than control cells after treatment with 100 nM insulin in conjugation with 0.5 mM palmitate. Conclusions: The obtained data demonstrated that TNF-α protein expression reduction improved insulin-stimulated Akt phosphorylation in the HepG2 cells and decreased lipidinduced insulin resistance of the diabetic hepatocytes.
Journal of Molecular Neuroscience
Several types of cellular proteins can be modified by farnesylation and nitrosylation, of which t... more Several types of cellular proteins can be modified by farnesylation and nitrosylation, of which the most significant is Ras. We used manumycin, a farnesyltransferase inhibitor, and L-NAME (Nω-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor, for characterization of Ras-dependent downstream targets activities. Our results suggest that change of the steady-state levels of nitric oxide and inhibition of farnesylation modified the activities of several transcription factors. We have found that the inhibition of farnesylation by manumycin decreased the DNA-binding activity of nuclear factor (NF)-κB, did not change the DNA-binding activities of STAT, Sp1, ATF-2, and CREB, and increased the activities of c-Fos, JunD, and c-Jun. Under such conditions, phosphorylation of Akt was decreased, whereas phosphorylation of extracellular signalregulated kinase (ERK) was increased and phosphorylation of JNK did not change. Furthermore, our results show that reduction of intracellular concentration of nitric oxides by L-NAME increases the activities of c-Fos, ATF-2 and JunD and decreases the activities of CREB, STAT, Sp1, and c-Jun. The activities of all of these transcription factors are restored to normal levels in the presence of manumycin, suggesting that simultaneous modifications of proteins by farnesylation and nitrosylation change the direction of Ras-controlled downstream pathways. Our results provide further evidence of the significance of posttranslational modifications of Ras for the specificity of transducing cascade networks and physiological outcome.
Journal of Food, Nutrition and Population Health, Sep 20, 2019
Additional file 2: Figure S2. Effect of LPS and glutamate on NO and IL-10 secretion. RAW 264.7 ce... more Additional file 2: Figure S2. Effect of LPS and glutamate on NO and IL-10 secretion. RAW 264.7 cells (RAW-NT) and mGluR5-transfected macrophages (RAW-mGluR5) (5–105 cells per well) were incubated with LPS (100 ng ⁄ ml) or glutamate (40 μM) for 24 h, followed by determination of NO (a) and IL-10 (b) secretion, as described in the "Methods" section. Data represented are mean ± SEM of results from four. separate experiments performed in duplicate. *P
Additional file 1: Figure S1. Expression of mGluR5, EAAT-2, PPAR-γ and HMGB1 proteins in control ... more Additional file 1: Figure S1. Expression of mGluR5, EAAT-2, PPAR-γ and HMGB1 proteins in control and mGluR5-transfected macrophages. RAW 264.7 cells (RAW-NT) and mGluR5-transfected macrophages (RAW-mGluR5) (5–105 cells per well) were incubated with LPS (100 ng ⁄ ml) or IL-10 (20 nM) for 24 h, followed by the determination of EAAT-2 (b), PPAR-γ (d) and HMGB1 (f) expression by western blot analysis, as described in the "Methods" section. (h) β-Actin was also visualized by Western blotting to confirm equal loading of the fractions. Data shown are representative of three independent experiments. Quantification of EAAT2 blots shown in c, *P
Additional file 3: Figure S3. Effect of mGluR5 transfection on the glutamate uptake by RAW 264.7 ... more Additional file 3: Figure S3. Effect of mGluR5 transfection on the glutamate uptake by RAW 264.7 cells. RAW 264.7 cells (RAW-NT) and mGluR5-transfected macrophages (RAW-mGluR5) (5–105 cells per well) were incubated with LPS (100 ng ⁄ ml) or IL-10 (20 nM) for 24 h, followed by the determination of glutamate in cell lysates, as described in the "Methods" section. Data represented are mean ± SEM of results from four separate experiments performed in duplicate. *P
Journal of World Mitochondria Society, 2015
Nobiletin (3’,4’,5,6,7,8-Hexamethoxyflavone) is a major component of citrus fruits. In mitochondr... more Nobiletin (3’,4’,5,6,7,8-Hexamethoxyflavone) is a major component of citrus fruits. In mitochondria, nobiletin decreases oxygen consumption in the presence of glutamate and malate and increases in the presence of succinate in both resting state and state 3 of electron transport chain. Affinity chromatography of mitochondrial membrane extracts revealed one major nobiletin-binding protein with 52 kD and several minor low molecular weight peptides. Western blotting experiments have shown that this protein is immunostained by the anti-NDUFV1 antibody. Spectroscopic analysis of the fraction demonstrated the UV-visible absorption spectrum characteristic of a [4Fe-4S] with an absorption shoulder around 400 nm. This protein complex catalyzes the NADH: ubiquinone reductase reaction, which was increased in the presence of nobiletin. We have found that this protein produces peroxides, and theformation of ROS was increased in the presence of rotenone. The addition of nobiletin significantly ...
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Papers by Davit Mikeladze