Laboratory of oxylipins
The research of the Laboratory is aimed at revealing the role of lipids as molecules that transmit information in the body regulation system. One of the directions is the study of signaling pathways that mediate the lipids ability to enhance proliferation or induce apoptosis, protect cells of the nervous system from the effects of damaging factors, induce cell differentiation and morphogenesis. Lipids are important regulators of a wide range of normal and pathological processes in the body, so the search for lipid molecules with more selective action is also at the center of the Laboratory's attention.
The main object of the Laboratory's research is natural oxylipins (prostaglandins, etc.), natural neurolypes (conjugates of fatty acids with biogenic amines, neurotransmitters and amino acids) and their synthetic analogues.
Earlier, the Laboratory staff (Bezuglov et al., 1995) suggested that the acylated derivatives of endogenous neurotransmitters can be a new family of bioregulators combining the properties of neuroactive lipids (anandamide) and classical neurotransmitters (dopamine, serotonin, etc.). Acyl-dopamines and derivatives of fatty acids with various amino acids were then found in the nervous and peripheral tissues of various organisms, including mammals. It turned out that these compounds have a wide range of biological effects that continue to be studied at the Laboratory.
The Laboratory discovered new ways of metabolizing acyl-dopamines and clarified some aspects of their biosynthesis. Also, the team showed that acyl-dopamines has a neuroprotective effect and it is able to induce apoptosis of the oncotransformed cells of various tissue origin in vitro, which indicates the large pharmacological potential of these substances. Now the researchers are investigating the mechanism of their toxic and differentiating effects on cancer cells, and also seek to increase the effectiveness of existing antitumor drugs.
To fight neurodegenerative diseases, an important socially significant problem, the Laboratory developed a strategy for searching for new neuroprotectors and protecting neurons from irreversible changes under the influence of stress. This approach is based on the use of the natural neuroactive lipids, peptides and other low-molecular bioregulators potential. Researchers managed to show that some modified acyl-dopamine are promising candidates for treatment of stroke consequences. In addition, the Laboratory is developing methods of directional delivery compounds to neurons capable to slowing down and reversing the neurodegenerative process.
Researchers of the Laboratory actively use modern methods of cell and molecular biology, fine organic synthesis, analytical chemistry and biochemistry.
The Laboratory cooperates with the Institute departments, as well as the Institute of Molecular Genetics of the Russian Academy of Sciences (RAS), the Mendeleev Russian Chemistry and Technology University, the Zakusov Institute of Pharmacology RAS, the Institute of Physiologically Active Substances RAS, the Koltsov Institute of Developmental Biology RAS, the Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, the Central University of Rajasthan (India), the Max Mousseron Institute of Biomolecules (France) etc.
The Laboratory was founded in 1990 on the basis of the Group of Prostaglandins and Leukotrienes.
- Neuroactive lipids and their role in normal and pathological processes.
- Mechanisms of lipid signals perception and intracellular transmission.
- The development of novel molecular instruments based of bioactive lipids (including fluorescent, biotynilated and isotope-labeled compounds).
- The development of new types of drugs, based on the conception of Information multifunctional compound molecules.
- The characterization of biosynthetic and catabolic pathways of N-acyl dopamines in rat liver, brain and spinal cord, as well as in freshwater hydra homogenate. The alternate pathways of N-acyl dopamines (sulfation, glucuronidation and catechol group oxidation) were identified for the first time.
- The identification of N-docosahexaenoyl dopamine in Hydra magnipapillata and H. Attenuate. The morphogenetic effect of acyl-dopamines and their ability to regulate regeneration processes in hydra were shown.
- It was shown for the first time that neurolypes from the group of N-acyl dopamine interfere in the death of neurons, save their functional properties in models of neurodegenerative processes, reduce the volume of neural tissue damage in focal ischemia, and increase survival in acute hypoxia and contribute to the preservation of cognitive functions in the posthypoxic period in experimental animals.
- The mechanism of signal transmission during the induction of apoptosis by N-acyl dopamine is established, the main proteins participating in this process are identified, including the cytoplasmic receptor, intracellular regulatory proteins, kinases and transcription factors.
- The ability of acyl-dopamine to induce the differentiation of oncotransformed cells was detected, new cell lines with increased resistance to acyl dopamine were obtained.
- A test system was developed to assess the hydrolytic stability of peptides and other compounds when administered orally on the basis of the rat gastrointestinal tract fragments.
- A new class of hybrid molecules peptolipins was synthesized, combining fragments of bioactive lipids, peptides and biogenic amines, which possess neuroprotective, vasoactive and anti-inflammatory effects.
- The development of a novel conception for pharmacological drug action prolongation using non-covalent complexes of protein with natural polysialic acid (size <=100 nm). A technology for the manufacturing of such nanocomplexes with genetical engineered interferons α2b and β1b, insulin and human G-CSF was developed, which is quite simple and productive. The experiments with cell cultures and animals confirmed the prolonged activity of the proteins inside nanocomplexes.
|Vladimir Bezuglov, D.Sc, professor||depart. email@example.com, |
|Natal'ja Greckaja, Ph.D.||s. r. firstname.lastname@example.org, |
|Mihail Bobrov, Ph.D.||s. r. f.|
|Mikhail Akimov, Ph.D.||s. r. email@example.com, |
|Elena Fomina-Ageeva, Ph.D.||r. f.|
|Galina Zinchenko||j. r. firstname.lastname@example.org, |
|Alina Lavrova||PhD email@example.com|
|Alina Gamisonia||PhD firstname.lastname@example.org, |
New fluorescent analogues of acyldopamines with the preserved the address moiety (2017-11-27)
New fluorescent analogues of natural acyldopamines mimicking residues of palmitic and oleic acids carrying the reporter BODIPY group at the distal end of molecule were synthesized. The specific uptake of mentioned compounds in rat pheochromocytoma PC12 cells was demonstrated and characteristics of this process were measured. Uptake rate of oleic analogue was more than three times as palmitic one. Synthesized compounds are ready to be used for investigation of acyldopamine transport in various cells of human or animal origin.
Modified peptides based on proglyprol structure with increased effectiveness (2016-03-29)
Hybrid compounds based on proglyprol (PGP) peptide carrying residues of docosahexaenoic acid and (or) dopamine were synthesized for the first time. Prepared compounds possess advanced neuroprotectory and anti-inflammatory activity and may consider as prototypes of novel pharmaceuticals.
- (2015). Cytotoxicity of endogenous lipids N-acyl dopamines and their possible metabolic derivatives for human cancer cell lines of different histological origin. Anticancer Res 35 (5), 2657–2661