Личная информация

Занимаюсь изучением биохимии ацилдофаминов и других сигнальных липидов (нейролипинов) и механизмов их действия в организме животных. В частности, веду исследования противоракового действия данных соединений (механизмы, универсальность).

Образование

Научные интересы

геронтология, теория эволюции, теоретическая биология, нейрохимия, биология липидов, онкология

Премии и заслуги

Диплом 1 степени за лучшую публикацию в журналах МАИК "Наука" (2006)

Диплом 3 степени на конкурсе молодых ученых в рамках VIII чтений памяти акад. Ю.А.Овчинникова (ИБХ РАН, 2009)

Основные научные результаты

1. Охарактеризованы пути биосинтеза и катаболизма N-ацилдофаминов в печени, головном и спинном мозге крысы и в гомогенате пресноводной гидры (http://goo.gl/Oifzb).
2. В организме пресноводных гидр Hydra attenuata и Hydra magnipapillata идентифицирован N­-докозагексаеноилдофамин.
3. Разработана тест-система для оценки гидролитической стабильности пептидов и других соединений при пероральном введении на основе фрагментов желудочно-кишечного тракта крысы.
4. Сформулирована гипотеза о существовании липидной противораковой подсистемы в организме животных, основанная на ацилдофаминах.

Гранты и проекты

Избранные публикации

1. Akimov M.G., Gretskaya N.M., Zinchenko G.N., Bezuglov V.V. (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), 2657–61 [+]

   Dopamine amides of long chain fatty acids are a family of endogenous mammalian lipids with an unknown function; they are anti-proliferative for the C6 glioblastoma cell line. To assess their possible anti-cancer activity we evaluated their cytotoxicity for a set of cancer cell lines.

   ID:1483
2. Akimov M.G., Bezuglov V.V. (2012). N-Acylated Dopamines: A New Life for the Old Dopamine. Dopamine: Functions, Regulation and Health Effects , [+]

   Обзор накопленных данных о биохимии и передаваемых сигналах сигнальных липидов семейства N-ацилдофаминов (глава в книге).

   ID:854
3. Акимов М.Г. (2009). Мембраны и рак. Липиды и рак. Очерки липидологии онкологического процесса , [+]

   Обзор роли мембран в развитии онкологического процесса (глава книги).

   ID:855
4. Akimov M.G., Nazimov I.V., Gretskaya N.M., Zinchenko G.N., Bezuglov V.V. (2009). Sulfation of N-acyl dopamines in rat tissues. Biochemistry Mosc. 74 (6), 681–5 [+]

   Sulfation of N-acyl dopamines has been shown for the first time in cytosolic fractions of rat liver and nervous system. Sulfation of dopamine amides of docosahexaenoic and oleic acids occurred in all tissues studied, N-arachidonoyl dopamine was sulfated in the liver and spinal cord, and N-stearoyl dopamine was sulfated only in the liver. Depending on the substrate and tissue, the sulfation activity varied from 0.5 to 3.5 nmol/min per mg total protein. Kinetic parameters of N-docosahexaenoyl dopamine sulfation in the brain were determined. The findings characterize the sulfation system as the most productive metabolic pathway of N-acyl dopamines, but the role of this system in the body is unclear because of high K(m) value.

   ID:572
5. Безуглов В.В., Грецкая Н.М., Клинов Д.В., Бобров М.Ю., Шибанова Е.Д., Акимов М.Г., Фомина-Агеева Е.В., Зинченко Г.Н., Баирамашвили Д.И., Мирошников А.И. (2009). Нанокомплексы рекомбинантных белков с полисиаловой кислотой. Получение, свойства и биологическая активность. Биоорг. хим. 35 (3), 350–356 ID:197
6. Akimov M.G., Nazimov I.V., Gretskaia N.M., Deigin V.I., Bezuglov V.V. (2009). [The study of peptide stability during hydrolysis by rat gastroenteric tract fragments]. Bioorg. Khim. 36 (6), 753–9 [+]

   The hydrolytic stability of therapeutic peptides such as dalargin, stemokin and some others, including cyclic tripeptides modified by ibuprofen and aspirin, was studied. Two experimental systems were used, one containing purified enzymes pepsin, trypsin and chymotrypsin and other based on fragments of rat stomach and ileum. It was found that linear peptides without D-aminoacids are hydrolyzed by fragments of stomach and ileum but resistant to hydrolysis with purified enzymes. The peptides with D-aminoacids and cyclic peptides are stable in all experimental conditions used, however, peptides modified with aspirin lost acetyl moiety of aspirin residue in acidic medium, the process is accelerated in presence of pepsin.

   ID:570
7. Ostroumova T.V., Markova L.N., Akimov M.G., Gretskaia N.M., Bezuglov V.V. (2009). [Docosahexaenoyl dopamine in freshwater hydra: effects on regeneration and metabolic changes]. Ontogenez 41 (3), 199–203 [+]

   The effects of docosahexaenoyl dopamine and docosahexaenoic acid on the regeneration of hydra gastric and basal fragments are studied. Docosahexaenoyl dopamine induced morphogenetic abnormalities such as single ectopic tentacles in the gastric region and projections in the gastric and basal regions. Docosahexaenoic acid had no effect on the morphogenesis except for a mild slowing of the regeneration rate. Since no hydrolysis of docosahexaenoyl dopamine was detected in hydra extract, it was assumed that the morphogenetic effect could be associated with the dopamine component of this complex.

   ID:571
8. Bezuglov V.V., Gretskaia N.M., Bobrov M.I.u., Akimov M.G., FominaAgeeva E.V., Zinchenko G.N., Bairamashvili D.I., Miroshnikov A.I. (2009). [Modification of recombinant proteins by covalent polysialation illustrated with the example of human insulin]. Bioorg. Khim. 35 (2), 274–8 [+]

   Methods of selective and nonselective covalent immobilization of genetically engineered proteins on molecules of natural polysialic acid are described by the example of human insulin. Such modification increases insulin lifetime in vivo.

   ID:573
9. Markova L.N., Ostroumova T.V., Akimov M.G., Bezuglov V.V. (2009). [N-arachidonoyl dopamine is a possible factor of the rate of tentacle formation in freshwater hydra]. Ontogenez 39 (1), 66–71 [+]

   The effect of N-arachidonoyl dopamine, haloperidol, and their mixture on the rate of tentacle formation was studied during regeneration of the gastral and basal fragments of freshwater hydra. Some concentrations of haloperidol inhibited the tentacle formation, which was more pronounced in the basal fragment. N-arachidonoyl dopamine accelerated the tentacle formation in both fragments, particularly, in the basal one (an inversion of the natural difference in the rate of tentacle formation between the gastral and basal fragments). After the exposure to the mixture of these drugs, the effects of each of them were observed. Mass spectrometry assay has demonstrated endogenous N-arachidonoyl dopamine in the intact hydra homogenate. The possible involvement of this acyl-neurotransmitter in the regulation of the rate of tentacle formation in regenerating hydra is discussed.

   ID:574
10. Akimov M.G., Gretskaia N.M., Shevchenko K.V., Shevchenko V.P., Miasoedov N.F., Bobrov M.I.u., Bezuglov V.V. (2009). [New aspects of biosynthesis and metabolism of N-acyldopamines in rat tissues]. Bioorg. Khim. 33 (6), 648–52 [+]

    Possible biosynthetic pathways of N-acyldopamines in rat tissues were compared. It was shown that an insignificant amount of the conjugation products was formed during the incubation of arachidonic acid and dopamine, whereas the substitution of tyrosine for dopamine resulted in the productive biosynthesis of N-arachidonoyldopamine. The biosynthesis presumably involves several closely conjugated enzymatic stages, and free fatty acids rather than their CoA esters served as the starting substrates. The decarboxylation stage probably precedes the stage of catechol system formation, because N-acetyltyramine (a probable intermediate) was easily oxidized by monophenol monooxygenase to N-acyldopamine, whereas N-acyltyrosine is hydrolyzed under these conditions. Biosynthesis of N-acyldopamines in a cell-free medium was accompanied by their methylation. The possibility of oxidative metabolism of N-acyldopamines, which could serve as co-substrates or inhibitors of different oxidoreductases, was shown for the first time.

    ID:575
11. Bezuglov V.V., Gretskaia N.M., Blazhenova A.V., Adrianova E.L., Akimov M.G., Bobrov M.I.u., Nazimov I.V., Kisel M.I., Sharko O.L., Novikov A.V., Krasnov N.V., Shevchenko V.P., Viunova T.V., Miasoedova N.F. (2009). [Arachidonoyl amino acids and arachidonoyl peptides: synthesis and properties]. Bioorg. Khim. 32 (3), 258–67 [+]

    N-Arachidonoyl (AA) derivatives of amino acids (glycine, phenylalanine, proline, valine, gamma-amino butyric acid (GABA), dihydroxyphenylalanine, tyrosine, tryptophan, and alanine) and peptides (Semax, MEHFPGP, and PGP) were synthesized in order to study the biological properties of acylamino acids. The mass spectra of all the compounds at atmospheric pressure electrospray ionization display the most intense peaks of protonated molecular ions; the detection limits for these compounds are 10 fmol per sample. AA-Gly showed the highest inhibitory activity toward fatty acid amide hydrolase from rat brain (IC50 6.5 microM) among all the acylamino acids studied. AA-Phe, AA-Tyr, and AA-GABA exhibited a weak but detectable inhibitory effect (IC50 55, 60, and 50 microM, respectively). The acylated amino acids themselves, except for AA-Gly, were stable to the hydrolysis by this enzyme. All the arachidonoylamino acids inhibited cabbage phospholipase D to various degrees; AA-GABA and AA-Phe proved to be the most active (IC50 20 and 27 microM, respectively). Attempts to detect the biosynthesis of AA-Tyr in homogenates of rat liver and nerve tissue showed no formation in vitro of either this acylamino acid or AA-dopamine and AA-Phe, the products of its metabolism. The highest contents of these metabolites were detected in liver homogenate and in the brain homogenate, respectively. Acylamino acids exert no cytotoxic effect toward the glioma C6 cells. It was shown that N-acylation of Semax with arachidonic acid results in enhancement of its hydrolytic stability and increases its affinity for the sites of specific binding in rat cerebellum membranes. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

    ID:576