Davit Mikeladze - Academia.edu (original) (raw)

Papers by Davit Mikeladze

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

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 ...

Georgian medical news, 2016

The present study investigated spatial working memory assessed in spontaneous alternation (SA) ta... more The present study investigated spatial working memory assessed in spontaneous alternation (SA) task and hippocampal glutamate and GABA release prior to, during, and after SA test in sham-operated and electrolytic medial septal (MS) lesioned rats. Also, have been investigated the effects of MS lesion on KCl-stimulated release of glutamate and GABA in the hippocampus. Behavioral study showed that electrolytic lesion of MS significantly impaired SA performance. Although both groups of animals had an insignificant rise in their respective hippocampal glutamate efflux during the SA, the rise of MS lesioned animals was blunted when compared with control animals. Hippocampal GABA levels did not change during behavioral testing in both groups. Most of control animals showed increase in KCl-stimulated glutamate release. By contrast, only one MS lesioned rat showed increase in glutamate release in response to KCl stimulation. Most of control and MS lesioned rats were non-responders in GABA re...

Journal of Biological Physics and Chemistry, 2008

Current Molecular Medicine, 2021

Cell Biochemistry and Function, 2019

Journal of Biological Physics and Chemistry, 2018

Journal of Biological Physics and Chemistry, 2016

Journal of Biological Physics and Chemistry

Reactive oxygen species (ROS) formed during ischaemia can activate the Ras signalling system, whi... more Reactive oxygen species (ROS) formed during ischaemia can activate the Ras signalling system, which amplifies the intracellular formation of ROS. Ras proteins induce senescence by altering the intracellular levels of ROS which leads to the impairment of homocysteine metabolism. The effects of the farnesyltransferase inhibitor, manumycin, were examined on ischaemia-evoked changed sulfur-containing amino acids. A rat four-vessel occlusion model was utilized to examine the effects of manumycin on cortical levels of homocysteine, methionine and cysteine. Cerebral ischaemia was induced by occlusion of the carotid arteries for 20 min in anaesthetized animals. Intraperitoneal injection of manumycin A (3 mg/kg body weight) was carried out 2 hours before anaesthesia. It was found that after ischaemia the quantities of methionine and homocysteine were decreased, whereas the amount of cysteine was increased. In the rats pretreated with manumycin, cerebral ischaemia does not change the content ...