zdorПроблемы здоровья и экологииHealth and Ecology Issues2220-09672708-6011Gomel State Medical University10.51523/2708-6011.2022-19-4-12zdor-2413Research ArticleЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНА И БИОЛОГИЯEXPERIMENTAL MEDICINE AND BIOLOGYРоль глутамата в энергетическом метаболизме тимусаRole of glutamate in thymic energy metabolismhttps://orcid.org/0000-0001-5871-440XНикитинаИ. А.NikitinaI. A.

Никитина Ирина Александровна, к.б.н., заведующийкафедрой биологической химии

Гомель

Irina A. Nikitina, Candidate of Biological Sciences, Headof the Department of Biological Chemistry

 Gomel

nikkitina@gmail.comГомельский государственный медицинский университетGomel State Medical University2022040120231948794Copyright © Никитина И.А., 20232023Никитина И.А.Nikitina I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.gsmu.by/jour/article/view/2413Цель исследования

Цель исследования. Провести анализ энергетической роли глутамата в тимоцитах и тканях тимуса на разных этапах его возрастной инволюции.

 Материалы и методы

 Материалы и методы. Исследования проведены на белых крысах-самцах. Состояние энергетического обмена определяли по скорости потребления кислорода тканями тимуса и тимоцитами с использованием полярографического метода.

Результаты

Результаты. Установлено, что в тканях тимуса 4-, 5- и 6-месячных крыс скорость потребления кислорода постоянна и значимо не изменяется в ответ на введение глутамата. Тимоциты — иммунокомпетентные клетки тимуса животных 3- и 8-месячного возраста, несмотря на сходные уровни потребления кислорода на эндогенных субстратах, по-разному реагируют на действие глутамата. В тимоцитах 3-месячных животных действие глутамата оказывает более выраженный стимулирующий эффект на биоэнергетические процессы по сравнению с 8-месячными. Есть основание полагать, что снижение эффективности действия глутамата по мере взросления животных обусловлено процессами возрастной инволюции тимуса.

Заключение

Заключение. Глутамат стимулирует аэробное дыхание в тимоцитах 3- и 8-месячных животных, при этом величина стимулирующего эффекта в тимоцитах более молодых животных выше. Одновременно с этим глутамат не вызывает значимых изменений скорости потребления кислорода в тканях тимуса 4-, 5- и 6-месячных животных.

Objective

Objective. To analyze the energetic role of glutamate in thymocytes and tissues of the thymus at different stages of its age-related involution.

Materials and methods

Materials and methods. The studies were performed on white male rats. The state of energy metabolism was determined by the rate of oxygen consumption by thymus tissues and thymocytes using a polarographic method.

Results

Results. It was found that in the thymus tissues of 4, 5 and 6-month-old rats the rate of oxygen consumption is constant and does not significantly change in response to glutamate administration. Thymocytes - the immunocompetent thymus cells of 3- and 8-month-old animals, despite similar levels of oxygen consumption on endogenous substrates, respond differently to glutamate action. In thymocytes of 3-month-old animals, the action of glutamate has a more pronounced stimulating effect on bioenergetic processes compared to 8-month-old animals. There is a reason to believe that the decrease in the efficiency of glutamate action as the animals grow older is caused by the processes of age-related involution of the thymus

Conclusion

Conclusion. Glutamate stimulates aerobic respiration in the thymocytes of 3- and 8-month-old animals, with a greater stimulating effect in the thymocytes of younger animals. At the same time, glutamate does not cause significant changes in the rate of oxygen consumption in the thymus tissues of 4-, 5-, and 6-month-old animals.

тимустканевое дыханиетимоцитыглутаматамиталинволюция тимусакислородполярографический методthymustissue respirationthymocytesglutamateamytalthymus involutionoxygenpolarographic methodReferencesKinnamon SC. Umami taste transduction mechanisms. Am J Clin Nutr. 2009;90(3):753S-755S. DOI: https://doi.org/10.3945/ajcn.2009.27462Km J Clin Nutr. 2009;90(3):753S-755S. DOI: https://doi.org/10.3945/ajcn.2009.27462KHermanussen M, García AP, Sunder M, Voigt M, Salazar V, Tresguerres JaF. Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite. Eur J Clin Nutr. 2006;60(1):25-31. DOI: https://doi.org/10.1038/sj.ejcn.1602263Hermanussen M, García AP, Sunder M, Voigt M, Salazar V, Tresguerres JaF. Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite. Eur J Clin Nutr. 2006;60(1):25-31. DOI: https://doi.org/10.1038/sj.ejcn.1602263Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I, Spanaki C. The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology (Basel). 2017;6(1):E11. DOI: https://doi.org/10.3390/biology6010011Plaitakis A, Kalef-Ezra E, Kotzamani D, Zaganas I, Spanaki C. The glutamate dehydrogenase pathway and its roles in cell and tissue biology in health and disease. Biology (Basel). 2017;6(1):E11. DOI: https://doi.org/10.3390/biology6010011Tsai PJ, Huang PC. Circadian variations in plasma and erythrocyte glutamate concentrations in adult men consuming a diet with and without added monosodium glutamate. J Nutr. 2000;130(4S Suppl):1002S-1004S. DOI: https://doi.org/10.1093/jn/130.4.1002STsai PJ, Huang PC. Circadian variations in plasma and erythrocyte glutamate concentrations in adult men consuming a diet with and without added monosodium glutamate. J Nutr. 2000;130(4S Suppl):1002S-1004S. DOI: https://doi.org/10.1093/jn/130.4.1002STomé D. The Roles of dietary glutamate in the intestine. Ann Nutr Metab. 2018;73(Suppl 5):15-20. DOI: https://doi.org/10.1159/000494777Tomé D. The Roles of dietary glutamate in the intestine. Ann Nutr Metab. 2018;73(Suppl 5):15-20. DOI: https://doi.org/10.1159/000494777Loï C, Cynober L. Glutamate: a safe nutrient, not just a simple additive. Ann Nutr Metab. 2022;78(3):133-146. DOI: https://doi.org/10.1159/000522482Loï C, Cynober L. Glutamate: a safe nutrient, not just a simple additive. Ann Nutr Metab. 2022;78(3):133-146. DOI: https://doi.org/10.1159/000522482Krishnamurthy RV, Suryawanshi YR, Essani K. Nitrogen isotopes provide clues to amino acid metabolism in human colorectal cancer cells. Sci Rep. 2017;7(1):2562. DOI: https://doi.org/10.1038/s41598-017-02793-yKrishnamurthy RV, Suryawanshi YR, Essani K. Nitrogen isotopes provide clues to amino acid metabolism in human colorectal cancer cells. Sci Rep. 2017;7(1):2562. DOI: https://doi.org/10.1038/s41598-017-02793-yСалига Н. Дія L-глутаміновоїкислоти та піридоксину на імунологічні й гематологічні показники за дії епінефрин-індукованого стресу в щурів. Науковий вісник Східноєвропейського національного університету імені Лесі Українки. Серія: Біологічні науки. 2019;3(387):131-136. DOI: https://doi.org/10.29038/2617-4723-2019-387-131-136Salyha, N. Effect of L-glutamic acid and pyridoxine on immunological and hematological parameters under the action of epinephrine- induced stress in rats. Lesya Ukrainka Eastern European National University Scientific Bulletin. Series: Biological Sciences. 2019;387(3):131-136. (In Ukr.) DOI: https://doi.org/10.29038/2617-4723-2019-387-131-136Piccirillo S, Castaldo P, Macrì ML, Amoroso S, Magi S. Glutamate as a potential “survival factor” in an in vitro model of neuronal hypoxia/reoxygenation injury: leading role of the Na+/ Ca2+ exchanger. Cell Death Dis. 2018;9(7):731. DOI: https://doi.org/10.1038/s41419-018-0784-6Piccirillo S, Castaldo P, Macrì ML, Amoroso S, Magi S. Glutamate as a potential “survival factor” in an in vitro model of neuronal hypoxia/reoxygenation injury: leading role of the Na+/ Ca2+ exchanger. Cell Death Dis. 2018;9(7):731. DOI: https://doi.org/10.1038/s41419-018-0784-6Dall’Asta V, Gazzola GC, Franchi-Gazzola R, Bussolati O, Longo N, Guidotti GG. Pathways of L-Glutamic acid transport in cultured human fibroblasts. J Biol Chem. 1983;258(10):6371- 6379. [дата обращения 2022 июль 06]. Режим доступа: https:// pubmed.ncbi.nlm.nih.gov/6133863Dall’Asta V, Gazzola GC, Franchi-Gazzola R, Bussolati O, Longo N, Guidotti GG. Pathways of L-Glutamic acid transport in cultured human fibroblasts. J Biol Chem. 1983;258(10):6371- 6379. [date of access 2022 July 06]. Available from: https:// pubmed.ncbi.nlm.nih.gov/6133863Magi S, Piccirillo S, Amoroso S. The dual face of glutamate: from a neurotoxin to a potential survival factormetabolic implications in health and disease. Cell Mol Life Sci. 2019;76(8):1473-1488. DOI: https://doi.org/10.1007/s00018-018-3002-x.Magi S, Piccirillo S, Amoroso S. The dual face of glutamate: from a neurotoxin to a potential survival factormetabolic implications in health and disease. Cell Mol Life Sci. 2019;76(8):1473-1488. DOI: https://doi.org/10.1007/s00018-018-3002-xTreberg JR, Banh S, Pandey U, Weihrauch D. Intertissue differences for the role of glutamate dehydrogenase in metabolism. Neurochem res. 2014;39(3):516-526. DOI: https://doi.org/10.1007/s11064-013-0998-zTreberg JR, Banh S, Pandey U, Weihrauch D. Intertissue differences for the role of glutamate dehydrogenase in metabolism. Neurochem Res. 2014;39(3):516-526. DOI: https://doi.org/10.1007/s11064-013-0998-zJungas RL, Halperin ML, Brosnan JT. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev. 1992;72(2):419-448. DOI: https://doi.org/10.1152/physrev.1992.72.2.419Jungas RL, Halperin ML, Brosnan JT. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev. 1992;72 (2):419-448. DOI: https://doi.org/10.1152/physrev.1992.72.2.419Burrin DG, Janeczko MJ, Stoll B. Emerging Aspects of Dietary Glutamate metabolism in the developing gut. Asia Pac J Clin Nutr. 2008;17(Suppl 1):368-371. DOI: https://doi.org/10.6133/APJCN.2008.17.S1.92Burrin DG, Janeczko MJ, Stoll B. Emerging aspects of dietary glutamate metabolism in the developing gut. Asia Pac J Clin Nutr. 2008;17(Suppl 1):368-371. DOI: https://doi.org/10.6133/APJCN.2008.17.S1.92Piccirillo S, Magi S, Castaldo P, Preziuso A, Lariccia V, Amoroso S. NCX and EAAT transporters in ischemia: At the crossroad between glutamate metabolism and cell survival. Cell Calcium. 2020;86:102160. DOI: https://doi.org/10.1016/j.ceca.2020.102160Piccirillo S, Magi S, Castaldo P, Preziuso A, Lariccia V, Amoroso S. NCX and EAAT transporters in ischemia: At the crossroad between glutamate metabolism and cell survival. Cell Calcium. 2020;86:102160. DOI: https://doi.org/10.1016/j.ceca.2020.102160Griffiths JB. The Effects of adapting human diploid cells to grow in glutamic acid media on cell morphology, growth and metabolism. J Cell Sci. 1973;12(2):617-629. DOI: https://doi.org/10.1242/jcs.12.2.617Griffiths JB. The Effects of adapting human diploid cells to grow in glutamic acid media on cell morphology, growth and metabolism. J Cell Sci. 1973;12(2):617-629. DOI: https://doi.org/10.1242/jcs.12.2.617King N, McGivan JD, Griffiths EJ, Halestrap AP, Suleiman MS. Glutamate loading protects freshly isolated and perfused adult cardiomyocytes against intracellular ROS generation. Journal of Molecular and Cellular Cardiology. 2003;35(8):975-984. DOI: https://doi.org/10.1016/S0022-2828(03)00182-2.King N, McGivan JD, Griffiths EJ, Halestrap AP, Suleiman MS. Glutamate loading protects freshly isolated and perfused adult cardiomyocytes against intracellular ROS generation. Journal of Molecular and Cellular Cardiology. 2003;35(8):975-984. DOI: https://doi.org/10.1016/S0022-2828(03)00182-2.Brelinska R, Malendowicz LK, Malinska A, Kowalska K. Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments. Biogerontology. 2008;9(2):93-108. DOI: https://doi.org/10.1007/s10522-007-9117-3Brelinska R, Malendowicz LK, Malinska A, Kowalska K. Characteristics of age-related changes in rat thymus: morphometric analysis and epithelial cell network in various thymic compartments. Biogerontology. 2008;9(2):93-108. DOI: https://doi.org/10.1007/s10522-007-9117-3Lewis MT, Levitsky Y, Bazil JN, Wiseman RW. Measuring mitochondrial function: from organelle to organism. Methods Mol Biol. 2022;2497:141-172. DOI: https://doi.org/10.1007/978-1-0716-2309-1_10Lewis MT, Levitsky Y, Bazil JN, Wiseman RW. Measuring mitochondrial function: from organelle to organism. Methods Mol Biol. 2022;2497:141-172. DOI: https://doi.org/10.1007/978-1-0716-2309-1_10Gnaiger E. Mitochondrial pathways and respiratory control: An Introduction to OXPHOS Analysis. 5th Ed. Bioenergetics Communications; 2020. DOI: https://doi.org/10.26124/bec:2020-0002Gnaiger E. Mitochondrial pathways and respiratory control: An Introduction to OXPHOS Analysis. 5th Ed. Bioenergetics Communications; 2020. DOI: https://doi.org/10.26124/bec:2020-0002Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992;284(Pt 1):1-13. DOI: https://doi.org/10.1042/bj2840001Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992;284(Pt 1):1-13. DOI: https://doi.org/10.1042/bj2840001Клаус Д, ред. Лимфоциты: методы. Пер с англ. Москва: Мир; 1990.Klaus D, ed. Limfocity: metody. Ttranslated from English. Moskov; 1990. (In Russ.)Wenchich L, Drahota Z, Honzík T, Hansíková H, Tesarová M, Zeman J, et al. Polarographic evaluation of mitochondrial enzymes activity in isolated mitochondria and in permeabilized human muscle cells with inherited mitochondrial defects. Physiol Res. 2003;52(6):781-788. [дата обращения 2022 июль 06]. Режим доступа: http://www.biomed.cas.cz/ physiolres/pdf/52/52_781.pdfWenchich L, Drahota Z, Honzík T, Hansíková H, Tesarová M, Zeman J, et al. Polarographic evaluation of mitochondrial enzymes activity in isolated mitochondria and in permeabilized human muscle cells with inherited mitochondrial defects. Physiol Res. 2003;52(6):781-788. [date of access 2022 July 06]. Available from: http://www.biomed.cas.cz/physiolres/ pdf/52/52_781.pdfКочетков ГА. Практическое руководство по энзимологии. 2-е изд, доп и перераб. Москва: Высшая школа; 1980.Kochetkov GA. Prakticheskoe rukovodstvo po jenzimologii. 2-e izd. dop. i pererab. Moskov; 1980. (In Russ.)Pon LA. Mitochondria. 2nd ed, add. and revised. Santa Barbara. Univ. of California: Еlsevier; 2006.Pon LA. Mitochondria. 2nd ed., add. and revised. Santa Barbara. Univ. of California: Еlsevier; 2006.Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992;284(Pt 1):1- 13. [дата обращения 2022 июль 06]. Режим доступа: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1132689/?page=1Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992;284(Pt 1):1- 13. [date of access 2022 July 06]. Available from: https://www. ncbi.nlm.nih.gov/pmc/articles/PMC1132689/?page=1Сергеенко СМ, Коваль АН, Жадейко РР, Никитина ИА, Грицук АИ. Тканевое дыхание миокарда, печени и тимуса белых крыс после внешнего облучения в дозе 1 Гр. В: Сб. науч. ст. Росс. науч. конф. с международным участием «Актуальные проблемы токсикологии и радиобиологии»; 2011 19- 20 мая; СПб.: ООО «Издательство Фолиант», 2011;141. [дата обращения 2022 июль 06]. Режим доступа: https://rep.polessu. by/bitstream/123456789/25837/1/Otsrochennye_jeffekty.pdfSergeenko SM, Koval’ AN, Zhadejko RR, Nikitina IA, Gricuk AN. Tkanevoe dyhanie miokarda, pecheni i timusa belyh krys posle vneshnego obluchenija v doze 1 Gr. V: Sb. nauch. st. Ross. nauch. konf. s mezhdunarodnym uchastiem «aktual’nye problemy toksikologii i radiobiologii»; 2011 19-20 maja; SPb.: OOO «Izdatel’stvo Foliant», 2011; 141. [date of access 2022 July 06]. Available from: https://rep.polessu.by/ bitstream/123456789/25837/1/Otsrochennye_jeffekty.pdf (In Russ.).Демьяненко СВ, Чистякова ВА, Водопьянов АС, Брень АБ. Возрастные изменения тимусзависимого звена иммунной системы. Журнал фундаментальной медицины и биологии. 2012;(1):17-29. [дата обращения 2022 июль 06]. Режим доступа: https://cyberleninka.ru/article/n/vozrastnyeizmeneniya-timuszavisimogo-zvena-immunnoy-sistemyDem’janenko SV, Chistjakova VA, Vodop’janova AS, Bren’ AB Age Changes Thymus-Dependent Part of Immune System. Zhuhurnal fundamental’noj medicyny i biologii. 2012;(1):17-29. [date of access 2022 July 06]. Available from: https://cyberleninka.ru/article/n/vozrastnye-izmeneniyatimuszavisimogo-zvena-immunnoy-sistemy (In Russ.).Brodsky VY, Malchenko LA, Butorina,NN, Lazarev Konchenko DS, Zvezdina ND, Dubovaya TK. Glutamic acid as enhancer of protein synthesis kinetics in hepatocytes from old rats. Biochemistry (Mosc). 2017;82(8):957-961. DOI: https://doi.org/10.1134/S0006297917080119Brodsky VY, Malchenko LA, Butorina NN, Lazarev (Konchenko) DS, Zvezdina ND, Dubovaya TK. Glutamic acid as enhancer of protein synthesis kinetics in hepatocytes from old rats. Biochemistry (Mosc). 2017;82(8):957-961. DOI: https://doi.org/10.1134/S0006297917080119Estonius M, Forsberg L, Danielsson O, Weinander R, Kelner MJ, Morgenstern R. Distribution of microsomal glutathione transferase 1 in mammalian tissues. Eur J Biochem. 1999;260(2):409-413. DOI: https://doi.org/10.1046/j.1432-1327.1999.00165.xEstonius M, Forsberg L, Danielsson O, Weinander R, Kelner MJ, Morgenstern R. Distribution of microsomal glutathione transferase 1 in mammalian tissues. Eur J Biochem. 1999;260(2):409-413. DOI: https://doi.org/10.1046/j.1432-1327.1999.00165.x

The authors declare that there are no conflicts of interest present.