Prof. Dr. Vladimir V. Bezuglov

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Academic Career Length

27Years (2000-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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1 February 2001 in Bioorganic & Medicinal Chemistry Letters

Journal Article

Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine

Vladimir V. Bezuglov

Mikhail Bobrov

Natalia Gretskaya

Alla Gonchar

Galina Zinchenko

Thierry Durand

12 February 2020 in Biomolecules

Journal Article

Arachidonoylcholine and Other Unsaturated Long-Chain Acylcholines Are Endogenous Modulators of the Acetylcholine Signaling System

Mikhail Akimov

Denis S. Kudryavtsev

ЕК

Елена Крюкова

Elena V. Fomina-Ageeva

Stanislav S. Zakharov

Vladimir V. Bezuglov

+13

Cholines acylated with unsaturated fatty acids are a recently discovered family of endogenous lipids. However, the data on the biological activity of acylcholines remain very limited. We hypothesized that acylcholines containing residues of arachidonic (AA-CHOL), oleic (Ol-CHOL), linoleic (Ln-CHOL), and docosahexaenoic (DHA-CHOL) acids act as modulators of the acetylcholine signaling system. In the radioligand binding assay, acylcholines showed inhibition in the micromolar range of both α7 neuronal nAChR overexpressed in GH4C1 cells and muscle type nAChR from Torpedo californica, as well as Lymnaea stagnalis acetylcholine binding protein. Functional response was checked in two cell lines endogenously expressing α7 nAChR. In SH-SY5Y cells, these compounds did not induce Ca²⁺ rise, but inhibited the acetylcholine-evoked Ca²⁺ rise with IC₅₀ 9 to 12 μM. In the A549 lung cancer cells, where α7 nAChR activation stimulates proliferation, Ol-CHOL, Ln-CHOL, and AA-CHOL dose-dependently decreased cell viability by up to 45%. AA-CHOL inhibited human erythrocyte acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BChE) by a mixed type mechanism with K_i= 16.7 ± 1.5 μM and αK_i= 51.4 ± 4.1 μM for AChE and K_i= 70.5 ± 6.3 μM and αK_i= 214 ± 17 μM for BChE, being a weak substrate of the last enzyme only, agrees with molecular docking results. Thus, long-chain unsaturated acylcholines could be viewed as endogenous modulators of the acetylcholine signaling system.

9 January 2021 in International Journal of Molecular Sciences

Journal Article

GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

Mikhail Akimov

Alina Gamisonia

Polina V. Dudina

Natalia M. Михайловна Gretskaya

Anastasia A. Gaydaryova

Vladimir V. Bezuglov

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca²⁺, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.

14 March 2023 in International Journal of Molecular Sciences

Journal Article

The Mechanisms of GPR55 Receptor Functional Selectivity during Apoptosis and Proliferation Regulation in Cancer Cells

Mikhail Akimov

Natalia M. Михайловна Gretskaya

GPR55 is a non-canonical cannabinoid receptor, important for cancer proliferation. Depending on the ligand, it induces either cell proliferation or death. The objective of the study was to establish the mechanisms of this multidirectional signaling. Using the CRISPR-Cas9 system, the GPR55, CB1, CB2, and GPR18 receptor knockouts of the MDA-MB-231 line were obtained. After the CB2 receptor knockout, the pro-apoptotic activity of the pro-apoptotic ligand docosahexaenoyl dopamine (DHA-DA) slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original cell line, the stimulatory effect of ML-184 was removed by the CB2 receptor blocker and by GPR55 receptor knockout. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 was additionally involved in the implementation of the pro-apoptotic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the pro-apoptotic action of DHA-DA, the elimination of Gα₁₃ led to a decrease in cytotoxicity. The obtained data provide novel details to the mechanism of the pro-proliferative action of GPR55.

26 March 2021 in Molecules

Journal Article

ACTH(6–9)PGP Peptide Protects SH-SY5Y Cells from H₂O₂, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Stimulation of Proliferation and Induction of Prosurvival-Related Genes

Mikhail Akimov

Elena V. Fomina-Ageeva

Stabilized melanocortin analog peptide ACTH(6–9)PGP (HFRWPGP) possesses a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we present a study of the proproliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6–9 (HFRW) linked with the peptide prolyine–glycyl–proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H₂O₂, tert-butyl hydroperoxide, and KCN and demonstrated proproliferative activity. The mechanism of its action was the modulation of proliferation-related NF-κB genes and stimulation of prosurvival NRF2-gene-related pathway, as well as a decrease in apoptosis.

20 April 2023 in Pharmaceutics

Journal Article

Multicomponent Lipid Nanoparticles for RNA Transfection

Natalia M. Михайловна Gretskaya

Mikhail Akimov

Dmitry E Andreev

Anton Vladlenovich Zalygin

Ekaterina Belitskaya

Vladimir V. Bezuglov

Despite the wide variety of available cationic lipid platforms for the delivery of nucleic acids into cells, the optimization of their composition has not lost its relevance. The purpose of this work was to develop multi-component cationic lipid nanoparticles (LNPs) with or without a hydrophobic core from natural lipids in order to evaluate the efficiency of LNPs with the widely used cationic lipoid DOTAP (1,2-dioleoyloxy-3-[trimethylammonium]-propane) and the previously unstudied oleoylcholine (Ol-Ch), as well as the ability of LNPs containing GM3 gangliosides to transfect cells with mRNA and siRNA. LNPs containing cationic lipids, phospholipids and cholesterol, and surfactants were prepared according to a three-stage procedure. The average size of the resulting LNPs was 176 nm (PDI 0.18). LNPs with DOTAP mesylate were more effective than those with Ol-Ch. Core LNPs demonstrated low transfection activity compared with bilayer LNPs. The type of phospholipid in LNPs was significant for the transfection of MDA-MB-231 and SW 620 cancer cells but not HEK 293T cells. LNPs with GM3 gangliosides were the most efficient for the delivery of mRNA to MDA-MB-231 cells and siRNA to SW620 cells. Thus, we developed a new lipid platform for the efficient delivery of RNA of various sizes to mammalian cells.

About Me

Education (degrees, dates, universities) M.Sc., 1972, Moscow Institute of Fine Chemical Technology, Moscow, Russia, lipid chemistry; Ph.D., 1982, thesis: “Fluorinated analogues of prostaglandins”, bioorganic chemistry. D.Sc., 1997, thesis: “Chemical modification of oxylipins and polyenoic fatty acids”, bioorganic chemistry. Career/Employment (employers, positions and dates) 1997 – present time, Head of Laboratory of Oxylipins, Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Laboratory of Oxylipins; 1987 - 1997; Head of Research Group; Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Group of Prostaglandins and Leukotrienes; 1984 - 1987; Senior Scientists; Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Laboratory of Lipid Chemistry; 1980 - 1984; Junior Scientists; Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Laboratory of Lipid Chemistry; 1972 - 1980; Researcher; Shemyakin - Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Laboratory of Lipid Chemistry. Specialization (I) main field: bioorganic chemistry (ii) other field: organic chemistry, biochemistry, medicinal chemistry (iii) current research interest: chemistry and biochemistry of eicosanoids, oxylipins, endocannabinoids, polyenoic fatty acids and their derivatives

Prof. Dr. Vladimir V. Bezuglov

Prof. Dr. Vladimir V. Bezuglov

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