vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.399vavilov-1595Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSЭкспрессия пальмитилтрансфераз в структурах мозга мышей с генетически детерминированной предрасположенностью к депрессивно-подобному поведениюExpression of palmitoyl transferases in brain structures of mice genetically predisposed to depressive-like behaviorКондауроваЕ. М.KondaurovaE. M.ИльчибаеваТ. В.IlchibaevaT. V.ЦыбкоА. С.TsybkoA. S.ПонимаскинЕ. Г.PonimaskinЕ. G.НауменкоВ. С.NaumenkoV. S.naumenko2002@mail.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics, SB RAS; Novosibirsk State UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics, SB RASRussian FederationИнститут клеточной нейрофизиологии, Высшая медицинская школа ГанновераГерманияInstitute of Cellular Neurophysiology, Hannover Medical High SchoolGermany201809082018225593599Copyright © Кондаурова Е.М., Ильчибаева Т.В., Цыбко А.С., Понимаскин Е.Г., Науменко В.С., 20182018Кондаурова Е.М., Ильчибаева Т.В., Цыбко А.С., Понимаскин Е.Г., Науменко В.С.Kondaurova E.M., Ilchibaeva T.V., Tsybko A.S., Ponimaskin Е.G., Naumenko V.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1595

Большинство сопряженных с G-белками мембранных рецепторов подвергается различным посттрансляционным модификациям. Среди таких модификаций – осуществляемое специализированны­ми ферментами пальмитилтрансферазами S-пальмитилирование. Оно представляет собой ковалентное присоединение длинной цепи жирной кислоты пальмитата к цистеиновым аминокислотным остаткам. Пальмитилирование может существенно влиять на функцию рецепторов, сопряженных с G-белками, модифицируя их стабильность, транспортировку и функциональную активность. Очевидно, что нарушения в работе этого класса рецепторов могут приводить к возникновению самых разнообразных психопатологий, включая депрессию. Тем не менее в настоящее время связи между пальмитилтрансферазами и депрессивно-подобным поведением не установлено. Нет данных и о регион-специфических особенностях экспрессии пальмитилтрансфераз в структурах мозга. В настоящей работе исследована экспрессия пальмитил­трансфераз ZDHHC5, ZDHHC9 и ZDHHC21 в структурах мозга мышей линии ASC с генетической предрасположенностью к депрессивно-подобному поведению по сравнению с мышами роди­тельской линии СВА, у которых не наблюдается депрессивно-по­добного поведения. Продемонстрированы регион-специфические особенности при иммунодетекции белков пальмитилтрансфераз. При детекции белка ZDHHC5 в среднем мозге выявлено две полосы массой 75 и 55 кДа. При иммунодетекции белка ZDHHC21 обнаружено две полосы: первая массой 27 кДа во фронтальной коре и среднем мозге, тогда как в гиппокампе антитела визуализировали полосу белка массой 32 кДа. При иммунодетекции белка ZDHHC9 выявлено по две полосы белка в среднем мозге и гиппокампе: первая полоса массой 46 кДа, вторая – 41 кДа. Однако мыши линии ASC практически не отличались от мышей СВА по экспрессии исследуемых пальмитилтрансфераз. Таким образом, нами впервые показаны регион-специфические особенности экспрессии исследованных пальмитилтрансфераз в структурах мозга. В то же время установлено, что генетически детерминированное депрессивноподобное поведение у мышей линии ASC не связано с изменениями экспрессии пальмитилтрансфераз ZDHHC5, ZDHHC9 и ZDHHC21.

Most G-coupled receptors undergo posttranslational modifications. Among these modifications is S-palmitoylation, carried out by specialized enzymes palmitoyl transferases. Palmitoylation is the covalent attachment of a long-chain fatty acid, palmitate, to cysteine residues. It can influence receptor stability, transportation, and function. Obviously, malfunction of G-protein coupled receptors can cause various psychic disor­ders, including depression. However, no association between palmitoyl transferases and depressive-like behavior has been found hitherto. There is no informa­tion on brain structure specific features of palmitoyl transferase expression either. Here we investigate the expression of ZDHHC5, ZDHHC9, and ZDHHC21 palmi­toyl transferases in brain structures of ASC mice with genetic predisposition to depressive-like behavior in comparison with “nondepressive” CBA mice. Several brain region-specific features were detected in the immunodetection of palmitoyl transferase proteins. Western blot of the ZDHHC5 protein in the midbrain revealed two bands at 75 kDa and 55 kDa. Immuno­detection of ZDHHC21 palmitoyl transferase revealed two bands. One of them was visualized at 27 kDa in the frontal cortex and midbrain. The other, at 32 kDa in the hippocampus. Probing for ZDHHC9 also showed two bands in each of the midbrain and hippocampus, at 46 and 41 kDa. However, the expression of all investigated palmitoyl transferases in ASC mice with depressive-like behavior was almost identical to those in CBA mice. Thus, it was the first detection of brain region-specific features of the expression of investigated palmitoyl transferases. However, the study demonstrates that the genetic predisposition to depression-like behavior in ASC mice is not associated with changes in ZDHHC5, ZDHHC9, or ZDHHC21 palmitoyl transferase expression.

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The serotonin hypothesis of major depression. Psychopharmacology: The Fourth Generation of Progress. Eds. E.E. Bloom, N.N. Kupfer. New York, 1995;933-944.Maes M., Meltzer H.Y. The serotonin hypothesis of major depression. Psychopharmacology: The Fourth Generation of Progress. Eds. E.E. Bloom, N.N. Kupfer. New York, 1995;933-944.Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., Popova N.K. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59-67. DOI S0306-4522(12)00390-9.Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., Popova N.K. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59-67. DOI S0306-4522(12)00390-9.Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., Popova N.K. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59-67. DOI S0306-4522(12)00390-9.Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., Popova N.K. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience. 2012;214:59-67. DOI S0306-4522(12)00390-9.Naumenko V.S., Kulikov A.V. Quantitative assay of 5-HT1A receptor gene expression in the brain. Molekulyarnaya Biologiya = Molecu¬lar Biology (Moscow). 2006;40(1):37-44. (in Russian)Naumenko V.S., Kulikov A.V. Quantitative assay of 5-HT1A receptor gene expression in the brain. Molekulyarnaya Biologiya = Molecu¬lar Biology (Moscow). 2006;40(1):37-44. (in Russian)Naumenko V.S., Kulikov A.V. Quantitative assay of 5-HT1A receptor gene expression in the brain. Molekulyarnaya Biologiya = Molecu¬lar Biology (Moscow). 2006;40(1):37-44. (in Russian)Naumenko V.S., Kulikov A.V. Quantitative assay of 5-HT1A receptor gene expression in the brain. Molekulyarnaya Biologiya = Molecu¬lar Biology (Moscow). 2006;40(1):37-44. (in Russian)Naumenko V.S., Osipova D.V., Kostina E.V., Kulikov A.V. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Meth. 2008;170(2):197-203. DOI S0165-0270(08)00044-7.Naumenko V.S., Osipova D.V., Kostina E.V., Kulikov A.V. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Meth. 2008;170(2):197-203. DOI S0165-0270(08)00044-7.Naumenko V.S., Osipova D.V., Kostina E.V., Kulikov A.V. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Meth. 2008;170(2):197-203. DOI S0165-0270(08)00044-7.Naumenko V.S., Osipova D.V., Kostina E.V., Kulikov A.V. Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain. J. Neurosci. Meth. 2008;170(2):197-203. DOI S0165-0270(08)00044-7.Neumeister A., Wood S., Bonne O., Nugent A.C., Luckenbaugh D.A., Young T., Bain E.E., Charney D.S., Drevets W.C. Reduced hippocampal volume in unmedicated, remitted patients with major depres-sion versus control subjects. Biol. Psychiatry. 2005;57(8):935-937. DOI 10.1016/j.biopsych.2005.01.016.Neumeister A., Wood S., Bonne O., Nugent A.C., Luckenbaugh D.A., Young T., Bain E.E., Charney D.S., Drevets W.C. Reduced hippocampal volume in unmedicated, remitted patients with major depres-sion versus control subjects. Biol. Psychiatry. 2005;57(8):935-937. 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The authors declare that there are no conflicts of interest present.