vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2018-15-2-199-206vestim-432Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEВЛИЯНИЕ АЛЬФА-КОБРАТОКСИНА НА ОКИСЛИТЕЛЬНЫЙ СТРЕСС, ИНДУЦИРОВАННЫЙ БЕССЫВОРОТОЧНОЙ СРЕДОЙ В КЛЕТКАХ ГЛИОМЫ С6EFFECT OF ALPHA-COBRATOXIN ON THE OXIDATIVE STRESS INDUCED BY A SERUM-FREE MEDIUM IN C6 GLIOMA CELLSТерпинскаяТ. И.TerpinskayaT. I.

Терпинская Татьяна Ильинична – канд. биол. наук,  вед. науч. сотрудник. 

ул. Академическая, 28, 220072, г. Минск.

 

Tatiana I. Terpinskaya – Ph. D. (Biol), Leading researcher.

28, Akademicheskaya Str., 220072, Minsk.

terpinskayat@mail.ruОсиповА. В.OsipovA. V.

Осипов Алексей Валерьевич – канд. хим. наук, ст.  науч.  сотрудник.  

ул.  Миклухо-Маклая, 16/10, 117997, г. Москва.

Alexey V. Osipov – Ph. D. (Chem.), Senior researcher. 

16/10, Miklouho-Maclai Str.,  117997, Moscow.

osipov-av@ya.ruКондрашоваС. Б.KondrashovaS. B.

Кондрашова Светлана Болеславовна – ст. науч. со– ст. науч. сотрудник.

ул. Академическая, 28, 220072, г. Минск.

 

Svetlana B. Kondrashova – Senior researcher. 

28, Akademicheskaya Str., 220072, Minsk.

Svetlana.condraschova2011@yandex.ruУлащикВ. С.UlashchykV. S.

Улащик Владимир Сергеевич – академик, д-р мед.  наук, гл. науч. сотрудник. 

ул. Академическая, 28, 220072, г. Минск.

 

Vladimir S. Ulashchyk – Academician, D. Sc. (Med.),  Professor, Chief researcher. 

28, Akademicheskaya Str., 220072, Minsk.

УткинЮ. Н.UtkinYu. N.

Уткин Юрий Николаевич – д-р хим. наук, гл. науч. сотрудник. 

ул.  Миклухо-Маклая, 16/10, 117997, г. Москва.

Yuri N. Utkin – D. Sc. (Chem.), Professor, Chief researcher.  

16/10, Miklouho-Maclai Str.,  117997, Moscow.

yutkin@yandex.ruИнститут физиологии НАН Беларуси.Institute of Physiology of the National Academy of Sciences of BelarusИнститут биоорганической химии им. М. М. Шемякина и Ю. А. Овчинникова РАН.Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences.201824062018152199206Copyright © Терпинская Т.И., Осипов А.В., Кондрашова С.Б., Улащик В.С., Уткин Ю.Н., 20182018Терпинская Т.И., Осипов А.В., Кондрашова С.Б., Улащик В.С., Уткин Ю.Н.Terpinskaya T.I., Osipov A.V., Kondrashova S.B., Ulashchyk V.S., Utkin Y.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/432

На  модели  клеток  глиомы  С6  показано,  что  роль  никотиновых  ацетилхолиновых  рецепторов  (нАХР) в регуляции окислительно-восстановительного баланса по-разному проявляется в различных условиях  культивирования. В бессывороточной среде ингибитор нАХР альфа-кобратоксин противодействует окислительному  стрессу, повышая активность супероксиддисмутазы и каталазы, уровень восстановленного глутатиона и снижая  концентрацию малонового диальдегида.

The model studies on C6 glioma cells showed that the role of nicotinic acetylcholine receptors (nAChR) in the  regulation of the redox balance varies under different cultivation conditions. In a serum-free medium, the inhibitor of nAXP  alpha-cobratoxin alleviates the oxidative stress that is manifested in an increase in the activity of superoxide dismutase and  catalase, the level of reduced glutathione and in a decrease in the concentration of malonic dialdehyde.

никотиновые  ацетилхолиновые  рецепторы  альфа-кобратоксин  супероксид  глутатион  супероксиддисмутазаnicotinic acetylcholine receptors alpha-cobratoxin superoxide glutathione superoxide dismutaseReferencesNicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells / F. Zanetti [et al.] // Free Radical Biology and Medicine. – 2014. – Vol. 76. – P. 173–184. DOI: 10.1016/j.freeradbiomed.2014.08.002Zanetti F., Giacomello M., Donati Y., Carnesecchi S., Frieden M., Barazzone-Argiroffo C. Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells. Free Radical Biology and Medicine, 2014, vol. 76, pp. 173-84. DOI: 10.1016/j.freeradbiomed.2014.08.002Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring / E. P. Conceição [et al.] // Food and Chemical Toxicology. – 2015. – Vol. 78. – P. 52–59. DOI: 10.1016/j.fct.2015.01.025Conceição E. P., Peixoto-Silva N., Pinheiro C. R., Oliveira E., Moura E. G., Lisboa P. C. Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring. Food and Chemical Toxicology, 2015, vol. 78, pp. 52-59. DOI: 10.1016/j.fct.2015.01.025Nicotine induces podocyte apoptosis through increasing oxidative stress / X. Lan [et al.] // PLoS One. – 2016. – Vol. 11, N 12. – P. e0167071. DOI: 10.1371/journal.pone.0167071Lan X., Lederman R., Eng J. M., Shoshtari S. S., Saleem M. A., Malhotra A., Singhal P. C. Nicotine induces podocyte apoptosis through increasing oxidative stress. PLoS One, 2016, vol. 11, no. 12, p. e0167071. DOI: 10.1371/journal.pone.0167071Niu, X.-M. Acetylcholine receptor pathway in lung cancer: new twists to an old story / X.-M. Niu, S. Lu // World J. of Clinical Oncology. – 2014. – Vol. 5, N 4. – P. 667–676. DOI: 10.5306/wjco.v5.i4.667Niu X.-M., Lu S. Acetylcholine receptor pathway in lung cancer: new twists to an old story. World Journal of Clinical Oncology, 2014, vol. 5, no. 4, pp. 667-676. DOI: 10.5306/wjco.v5.i4.667Ion channals gated by acetilcholin by acetylcholine and serotonin: structures, biology, and drug discovery / Z. S. Wu [et al.] // Acta Pharmacologica Sinica. – 2015. – Vol. 36, N 8. – P. 895–907. DOI: 10.1038/aps.2015.66Wu Z. S., Cheng H., Jiang Y., Melcher K., Xu H. E. Ion channals gated by acetilcholin by acetylcholine and serotonin: structures, biology, and drug discovery.  Acta Pharmacologica Sinica, 2015, vol. 36, no. 8, pp. 895-907. DOI: 10.1038/ aps.2015.66Nicotine exposure and the progression of chronic kidney disease: role of the α7-nicotinic acetylcholine receptor / G. Rezonzew [et al.] // Amer. J. of Physiology-Renal Physiology. – 2012. – Vol. 303, N 2. – P. F304–F312. DOI: 10.1152/ajprenal.00661.2011Rezonzew G., Chumley P., Feng W., Hua P., Siegal G. P., Jaimes E. A. Nicotine exposure and the progression of chronic kidney disease: role of the α7-nicotinic acetylcholine receptor. American Journal of Physiology-Renal Physiology, 2012, vol. 303, no. 2, pp. F304-F312. DOI: 10.1152/ajprenal.00661.2011Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar β amyloid peptide (1-42)-stimulated microglia / J. H. Moon [et al.] // Experimental and Molecular Medicine. – 2008. – Vol. 40, N 1. – P. 11–18. DOI: 10.3858/emm.2008.40.1.11Moon J. H., Kim S. Y., Lee H. G., Kim S. U., Lee Y. B. Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar β amyloid peptide (1-42)-stimulated microglia. Experimental and Molecular Medicine, 2008, vol. 40, no. 1, pp. 11-18. DOI: 10.3858/emm.2008.40.1.11Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicity / A. V. Kamynina [et al.] // Intern. J. of Biochemistry and Cell Biology. – 2013. – Vol. 45, N 4. – P. 899–907. DOI: 10.1016/j.biocel.2013.01.011Kamynina A. V., Holmstrom K. M., Koroev D. O., Volpina O. M., Abramov A. Y. Acetylcholine and antibodies against the acetylcholine receptor protect neurons and astrocytes against beta-amyloid toxicityInternational. Journal of Biochemistry and Cell Biology, 2013, vol. 45, no. 4, pp. 899-907. DOI: 10.1016/j.biocel.2013.01.011Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: implications for Parkinson’s disease / Y. Liu [et al.] // Neuropharmacology. – 2015. – Vol. 91. – P. 87–96. DOI: 10.1016/j.neuropharm.2014.11.028Liu Y., Zeng X., Hui Y., Zhu C., Wu J., Taylor D. H., Ji J., Fan W., Huang Z., Hu J. Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: implications for Parkinson’s disease. Neuropharmacology, 2015, vol. 91, pp. 87-96. DOI: 10.1016/j.neuropharm.2014.11.028Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture / Z. Han [et al.] // J. of Neurochemistry. – 2014. – Vol. 131, N 4. – P. 498–508. DOI: 10.1111/jnc.12817Han Z., Li L., Wang L., Degos V., Maze M., Su H. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture. Journal of Neuroche- mistry, 2014, vol. 131, no. 4, pp. 498-508. DOI: 10.1111/jnc.12817Nirthanan, S. Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on / S. Nirthanan, M. C. Gwee // J. of Pharmacological Sciences. – 2004. – Vol. 94, N 1. – P. 1–17. DOI: 10.1254/jphs.94.1Nirthanan S., Gwee M. C. Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on. Journal of Pharmacological Sciences, 2004, vol. 94, no. 1, pp. 1-17. DOI: 10.1254/jphs.94.1Wang, Z. F. Huperzine A protects C6 rat glioma cells against oxygen-glucose deprivation-induced injury / Z. F. Wang, X. C. Tang // FEBS Letters. – 2007. – Vol. 581, N 4. – P. 596–602. DOI: 10.1016/j.febslet.2007.01.016Wang Z. F., Tang X. C. Huperzine A protects C6 rat glioma cells against oxygen-glucose deprivation-induced injury. FEBS Letters, 2007, vol. 581, no. 4, pp. 596-602. DOI: 10.1016/j.febslet.2007.01.016Niranjan, R. Melatonin attenuated mediators of neuroinflammation and alpha-7 nicotinic acetylcholine receptor mRNA expression in lipopolysaccharide (LPS) stimulated rat astrocytoma cells, C6 / R. Niranjan, C. Nath, R. Shukla // Free Radical Research. – 2012. – Vol. 46, N 9. – P. 1167–1177. DOI: 10.3109/10715762.2012.697626Niranjan R., Nath C., Shukla R. Melatonin attenuated mediators of neuroinflammation and alpha-7 nicotinic acetylcholine receptor mRNA expression in lipopolysaccharide (LPS) stimulated rat astrocytoma cells, C6. Free Radical Research, 2012, vol. 46, no. 9, pp. 1167-1177. DOI: 10.3109/10715762.2012.697626Dimeric α-cobratoxin X-ray structure: localization of intermolecular disulfi des and possible mode of binding to nicoα-cobratoxin X-ray structure: localization of intermolecular disulfi des and possible mode of binding to nico-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors / A. V. Osipov [et al.] // J. of Biological Chemistry. – 2012. – Vol. 287. – P. 6725–6734. DOI: 10.1074/jbc.M111.322313Osipov A. V., Rucktooa P., Kasheverov I. E., Filkin S. Y., Starkov V. G., Andreeva T. V., Sixma T. K., Bertrand D., Utkin Y. N., Tsetlin V. I. Dimeric α-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. Journal of Biological Chemistry, 2012, vol. 287, pp. 6725-6734. DOI: 10.1074/ jbc.M111.322313Метод определения активности каталазы / М. А. Королюк [и др.] // Лаб. дело. – 1988. – № 1. – С. 16–19.Korolyuk M. A., Ivanova L. I., Maiorova I. G., Tokarev V. E. Method for determination of catalase activity. Laboratornoye delo [Laboratory Work], 1988, no. 1, pp. 16-19 (in Russian).Костюк, В. А. Простой и чувствительный метод определения активности супероксиддисмутазы, основанный на реакции окисления кверцетина / В. А. Костюк, А. И. Потапович, Ж. В. Ковалева // Вопр. мед. химии. – 1990. – Т. 36, № 2. – С. 88–91.Kostyuk V. A., Potapovich A. I., Kovaleva Zh. V. A simple and sensitive method for determining the activity of superoxide dismutase, based on the reaction of quercetin oxidation. Voprosy meditsinskoi khimii [Questions of Medical Chemistry], 1990, vol. 36, no. 2, pp. 88-91 (in Russian).Oxy-radical metabolism and control of tumour growth / T. Galeotti [et al.] // Xenobiotica. – 1991. – Vol. 21, N 8. – P. 1041–1051. DOI: 10.3109/00498259109039544Galeotti T., Masotti L., Borrello S., Casali E. Oxy-radical metabolism and control of tumour growth. Xenobiotica, 1991, vol. 21, no. 8, pp. 1041-1051. DOI: 10.3109/00498259109039544Разыграев, А. В. Определение глутатионпероксидазной активности в сыворотке крови человека с использованием пероксида водорода и 5,5′-дитиобис (2-нитробензойной кислоты) / А. В. Разыграев А. В. Арутюнян // Клин. лаб. диагностика. – 2006. – № 6. – С. 13–16.Razygraev A. V., Arutyunyan A. V. Determination of human serum glutathione peroxidase activity, by using hydrogen peroxide and 5,5′-dithio-bis (2-nitrobenzoic acid). Klinicheskaya laboratornaya diagnostika [Russian Clinical Laboratory Diagnostics], 2006, no. 6, pp. 13-16 (in Russian).Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate through increased mitochondrial translocation of protein kinase Cα in C2C12 myocytes / Y. Wang [et al.] // Biochemical Pharmacology. – 2006. – Vol. 72, N 7. – Р. 881–892. DOI: 10.1016/j.bcp.2006.06.032Wang Y., Biswas G., Prabu S. K., Avadhani N. G. Modulation of mitochondrial metabolic function by phorbol 12-myristate 13-acetate through increased mitochondrial translocation of protein kinase Cα in C2C12 myocytes. Biochemical Pharmacology, 2006, vol. 72, no. 7, pp. 881-892. DOI: 10.1016/j.bcp.2006.06.032The protein kinase C inhibitor Aeb071 (sotrastaurin) modulates migration and superoxide anion production by human neutrophils in vitro / F. Capsoni [et al.] // Intern. J. of Immunopathology and Pharmacology. – 2012. – Vol. 25, N 3. – P. 617– 626. DOI: 10.1177/039463201202500308Capsoni F., Ongari A. M., Reali E., Bosè F., Altomare G. F. The protein kinase C inhibitor Aeb071 (sotrastaurin) modulates migration and superoxide anion production by human neutrophils in vitro. International Journal of Immunopatho- logy and Pharmacology, 2012, vol. 25, no. 3, pp. 617-626. DOI: 10.1177/039463201202500308Nicotine-induced apoptosis in human renal proximal tubular epithelial cells / C. S. Kim [et al.] // PLoS One. – 2016. – Vol. 11, N 3. – P. e0152591. DOI: 10.1371/journal.pone.0152591Kim C. S., Choi J. S., Joo S. Y., Bae E. H., Ma S. K., Lee J., Kim S. W. Nicotine-induced apoptosis in human renal proximal tubular epithelial cells.  PLoS One, 2016, vol. 11, no. 3, p. e0152591. DOI: 10.1371/journal.pone.0152591Steinberg, S. F. Mechanisms for redox-regulation of protein kinase C / S. F. Steinberg // Frontiers in Pharmacology. – 2015. – Vol. 6. – P. 128. DOI: 10.3389/fphar.2015.00128Steinberg S. F. Mechanisms for redox-regulation of protein kinase C. Frontiers in Pharmacology, 2015, vol. 6, p. 128. https://doi.org/10.3389/fphar.2015.00128Shen, J. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system / J. Shen, J. L. Yakel // Acta Pharmacologica Sinica. – 2009. – Vol. 30, N 6. – Р. 673–680. DOI: 10.1038/aps.2009.64Shen J., Yakel J. L. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system.  Acta Pharmacologica Sinica, 2009, vol. 30, no. 6, pp. 673-680. DOI: 10.1038/aps.2009.64Transforming growth factor-beta and oxidative stress interplay: implications in tumorigenesis and cancer progression / J. Krstić [et al.] // Oxidative Medicine and Cellular Longevity. – 2015. – Vol. 2015. – 15 p. DOI: 10.1155/2015/654594Krstić J., Trivanović D., Mojsilović S., Santibanez J. F. Transforming growth factor-beta and oxidative stress interplay: implications in tumorigenesis and cancer progression. Oxidative Medicine and Cellular Longevity, 2015, vol. 2015. 15 p. https://doi.org/10.1155/2015/654594Fibroblast growth factor 21 protects the heart from oxidative stress / A. Planavila [et al.] // Cardiovascular Research. – 2014. – Vol. 106, N 1. – P. 19–31. DOI: 10.1093/cvr/cvu263Planavila A., Redondo-Angulo I., Ribas F., Garrabou G., Casademont J., Giralt M., Villarroya F. Fibroblast growth factor 21 protects the heart from oxidative stress.  Cardiovascular Research, 2014, vol. 106, no. 1, pp. 19-31. DOI: 10.1093/cvr/cvu263Arda-Pirincci, P. The role of epidermal growth factor in prevention of oxidative injury and apoptosis induced by intestinal ischemia/reperfusion in rats / P. Arda-Pirincci, S. Bolkent // Acta Histochemica. – 2014. – Vol. 116, N 1. – P. 167– 175. DOI: 10.1016/j.acthis.2013.07.005Arda-Pirincci P., Bolkent S. The role of epidermal growth factor in prevention of oxidative injury and apoptosis induced by intestinal ischemia/reperfusion in rats. Acta Histochemica, 2014, vol. 16, no. 1, pp. 167-175. DOI: 10.1016/j.acthis.2013.07.005Lushchak, V. I. Free radicals, reactive oxygen species, oxidative stress and its classification / V. I. Lushchak // Chemico-Biological Interactions. – 2014. – Vol. 224. – P. 164–175. DOI: 10.1016/j.cbi.2014.10.016Lushchak V. I. Free radicals, reactive oxygen species, oxidative stress and its classification. Chemico-Biological Interactions, 2014, vol. 224, pp. 164-175. DOI: 10.1016/j.cbi.2014.10.016In vitro effect of sodium fluoride on malondialdehyde concentration and on superoxide dismutase, catalase, and glutathione peroxidase in human erythrocytes / J. Gutiérrez-Salinas [et al.] // The Scientific World J. – 2013. – Vol. 2013. – 7 p. DOI: 10.1155/2013/864718Gutiérrez-Salinas J., García-Ortíz L., Morales González J. A., Hernández-Rodríguez S., Ramírez-García S., NúñezRamos N. R., Madrigal-Santillán E. In vitro effect of sodium fluoride on malondialdehyde concentration and on superoxide dismutase, catalase, and glutathione peroxidase in human erythrocytes. Scientific World Journal, 2013, vol. 2013. 7 p. DOI: 10.1155/2013/864718

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