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Синергидные нейропротекторные эффекты тиамина, пиридоксина и цианокобаламина в рамках протеома человека
Громова О.А., Торшин И.Ю., Прокопович О.А. Синергидные нейропротекторные эффекты тиамина, пиридоксина и цианокобаламина в рамках протеома человека. Consilium Medicum. Неврология и Ревматология (Прил.). 2016; 2: 76–84.
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Gromova O.A., Torshin I.Yu., Prokopovich O.A. Synergistic neuroprotective effects of thiamine, pyridoxine and cyanocobalamin within the human proteome. Consilium Medicum. Neurology and Rheumatology (Suppl.). 2016; 2: 76–84.
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Аннотация
Витамины группы В характеризуются нейропротекторными эффектами. Механизмы синергидного действия различных комбинаций витаминов недостаточно изучены. В настоящем исследовании в геномных и протеомных базах данных были найдены белки, активность или уровни которых взаимосвязаны с обеспеченностью организма витаминами В1 (тиамин), В6 (пиридоксин) и В12 (цианокобаламин). Системно-биологический анализ показал, что тиамин необходим для синтеза аденозинтрифосфорной кислоты – АТФ (в том числе посредством метаболизма глюкозы, липидов и аминокислот с разветвленной цепью), кроветворения и для роста и поддержания структуры нейронов. Пиридоксинзависимые белки протеома необходимы для метаболизма аминокислот, синтеза АТФ, нейротрансмиттеров и мембран нейронов. Витамин В12 необходим для метаболизма липидов, кроветворения и проявляет нейропротекторный и нейротрофический эффекты. Выявлены многочисленные синергидные взаимодействия витаминов В1, В6, В12 на молекулярном уровне, включающие метаболизм аминокислот, углеводов, липидов, формирование структур нейронов, кроветворение, синтез АТФ и др. Установленные механизмы синергизма витаминов В1, В6, В12 на молекулярном уровне имеют фундаментальное значение для нейропротекции и профилактики цереброваскулярной патологии.
Ключевые слова: тиамин, пиридоксин, цианокобаламин, синергизм, биоинформатика, нейропротекция, Нейробион.
Ключевые слова: тиамин, пиридоксин, цианокобаламин, синергизм, биоинформатика, нейропротекция, Нейробион.
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B vitamins are characterized neuroprotective effects. Mechanisms of action of synergistic combinations of various vitamins are insufficiently studied. In this study, protein, activity or levels which are interconnected with the security body with vitamins B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamin) were found in genomic and proteomic databases. Systemically-biological analysis showed that the thiamine necessary for the synthesis of adenosine triphosphate – ATP (by means including glucose metabolism, lipid and branched chain amino acids), and hemopoietic growth and maintenance of neuronal structure. Piridoksinzavisimye proteome proteins necessary for the metabolism of amino acids, ATP synthesis of neurotransmitters and neuronal membranes. Vitamin B12 is needed for the metabolism of lipids, hematopoiesis and shows neuroprotective and neurotrophic effects. Numerous synergistic interactions of vitamins B1, B6, B12, at the molecular level, including the metabolism of amino acids, carbohydrates, lipids, forming structures of neurons, blood, ATP synthesis, and others are examined. The established mechanisms of vitamins B1 synergies, B6, B12, at the molecular level are of fundamental importance for neuroprotection and prevention of cerebrovascular disease.
Key words: thiamine, pyridoxine, cyanocobalamin, synergies, bioinformatics, neuroprotection, Neyrobion.
Полный текст
Список литературы
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12. Oka T, Komori N, Kuwahata M et al. Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver. Biochem J 1995; 309 (Pt 1): 243–8.
13. Isola LM, Zhou SL, Kiang CL et al. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. Proc Natl Acad Sci USA 1995; 92 (21): 9866–70.
14. Almeida MR, Mabasa L, Crane C et al. Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring. Mol Nutr Food Res 2016; 60 (7): 1615–24 DOI.
15. Rai NK, Ashok A, Rai A et al. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina. Toxicol Appl Pharmacol 2013; 273 (2): 242–58 DOI.
16. Castegna A, Palmieri L, Spera I et al. Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience 2011; 185: 97–105 DOI.
17. Yang TY, Chang GC, Hsu SL et al. Effect of folic acid and vitamin B12 on pemetrexed antifolate chemotherapy in nutrient lung cancer cells. Biomed Res Int 2013; 2013: 389046. DOI: 10.1155/2013/389046.
18. Bauer JA, Morrison BH, Grane RW et al. Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin. J Natl Cancer Inst 2002; 94 (13): 1010–9.
19. Shimizu N, Hamazoe R, Kanayama H et al. Experimental study of antitumor effect of methyl-B12. Oncology 1987; 44 (3): 169–73.
2. Ребров В.Г., Громова О.А. Витамины, макро- и микроэлементы. М.: ГЭОТАР-МЕД, 2008. / Rebrov V.G., Gromova O.A. Vitaminy, makro- i mikroelementy. M.: GEOTAR-MED, 2008. [in Russian]
3. Torshin I.Yu. Sensing the change from molecular genetics to personalized medicine. NY: Nova Biomedical Books, 2009.
4. Forny P, Froese DS, Suormala T et al. Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. Hum Mutat 2014; 35 (12): 1449–58.
5. Ambrosch A, Dierkes J, Lobmann R et al. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabet Med 2001; 18 (3): 185–92.
6. Midttun O, Hustad S, Schneede J et al. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 2007; 86 (1): 131–8.
7. Bettendorff L, Wins P, Lesourd M. Subcellular localization and compartmentation of thiamine derivatives in rat brain. Biochim Biophys Acta 1994; 1222 (1): 1–6.
8. Fournier H, Butterworth RF. Effects of maternal thiamine deficiency on the development of thiamine-dependent enzymes in regions of the rat brain. Neurochem Int 1989; 15 (4): 439–44.
9. Kimura S, Ohtuki N, Nezu A et al. Clinical and radiologic improvements in mitochondrial encephalomyelopathy following sodium dichloroacetate therapy. Brain Dev 1997; 19 (8): 535–40.
10. Sterzel RB, Semar M, Lonergan ET et al. Relationship of nervous tissue transketolase to the neuropathy in chronic uremia. J Clin Invest 1971; 50 (11): 2295–304.
11. Roomi MW, Ishaque A, Khan NR, Eylar EH. Glycoproteins and albumin in peripheral nerve myelin. J Neurochem 1978; 31 (1): 375–9.
12. Oka T, Komori N, Kuwahata M et al. Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver. Biochem J 1995; 309 (Pt 1): 243–8.
13. Isola LM, Zhou SL, Kiang CL et al. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. Proc Natl Acad Sci USA 1995; 92 (21): 9866–70.
14. Almeida MR, Mabasa L, Crane C et al. Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring. Mol Nutr Food Res 2016; 60 (7): 1615–24 DOI.
15. Rai NK, Ashok A, Rai A et al. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina. Toxicol Appl Pharmacol 2013; 273 (2): 242–58 DOI.
16. Castegna A, Palmieri L, Spera I et al. Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience 2011; 185: 97–105 DOI.
17. Yang TY, Chang GC, Hsu SL et al. Effect of folic acid and vitamin B12 on pemetrexed antifolate chemotherapy in nutrient lung cancer cells. Biomed Res Int 2013; 2013: 389046. DOI: 10.1155/2013/389046.
18. Bauer JA, Morrison BH, Grane RW et al. Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin. J Natl Cancer Inst 2002; 94 (13): 1010–9.
19. Shimizu N, Hamazoe R, Kanayama H et al. Experimental study of antitumor effect of methyl-B12. Oncology 1987; 44 (3): 169–73.
________________________________________________
1. Torshin IY, Gromova OA. Magnesium and pyridoxine: fundamental studies and clinical practice. Nova Science Publishers, 2011.
2. Rebrov V.G., Gromova O.A. Vitaminy, makro- i mikroelementy. M.: GEOTAR-MED, 2008. [in Russian]
3. Torshin I.Yu. Sensing the change from molecular genetics to personalized medicine. NY: Nova Biomedical Books, 2009.
4. Forny P, Froese DS, Suormala T et al. Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. Hum Mutat 2014; 35 (12): 1449–58.
5. Ambrosch A, Dierkes J, Lobmann R et al. Relation between homocysteinaemia and diabetic neuropathy in patients with Type 2 diabetes mellitus. Diabet Med 2001; 18 (3): 185–92.
6. Midttun O, Hustad S, Schneede J et al. Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 2007; 86 (1): 131–8.
7. Bettendorff L, Wins P, Lesourd M. Subcellular localization and compartmentation of thiamine derivatives in rat brain. Biochim Biophys Acta 1994; 1222 (1): 1–6.
8. Fournier H, Butterworth RF. Effects of maternal thiamine deficiency on the development of thiamine-dependent enzymes in regions of the rat brain. Neurochem Int 1989; 15 (4): 439–44.
9. Kimura S, Ohtuki N, Nezu A et al. Clinical and radiologic improvements in mitochondrial encephalomyelopathy following sodium dichloroacetate therapy. Brain Dev 1997; 19 (8): 535–40.
10. Sterzel RB, Semar M, Lonergan ET et al. Relationship of nervous tissue transketolase to the neuropathy in chronic uremia. J Clin Invest 1971; 50 (11): 2295–304.
11. Roomi MW, Ishaque A, Khan NR, Eylar EH. Glycoproteins and albumin in peripheral nerve myelin. J Neurochem 1978; 31 (1): 375–9.
12. Oka T, Komori N, Kuwahata M et al. Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver. Biochem J 1995; 309 (Pt 1): 243–8.
13. Isola LM, Zhou SL, Kiang CL et al. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. Proc Natl Acad Sci USA 1995; 92 (21): 9866–70.
14. Almeida MR, Mabasa L, Crane C et al. Maternal vitamin B6 deficient or supplemented diets on expression of genes related to GABAergic, serotonergic, or glutamatergic pathways in hippocampus of rat dams and their offspring. Mol Nutr Food Res 2016; 60 (7): 1615–24 DOI.
15. Rai NK, Ashok A, Rai A et al. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina. Toxicol Appl Pharmacol 2013; 273 (2): 242–58 DOI.
16. Castegna A, Palmieri L, Spera I et al. Oxidative stress and reduced glutamine synthetase activity in the absence of inflammation in the cortex of mice with experimental allergic encephalomyelitis. Neuroscience 2011; 185: 97–105 DOI.
17. Yang TY, Chang GC, Hsu SL et al. Effect of folic acid and vitamin B12 on pemetrexed antifolate chemotherapy in nutrient lung cancer cells. Biomed Res Int 2013; 2013: 389046. DOI: 10.1155/2013/389046.
18. Bauer JA, Morrison BH, Grane RW et al. Effects of interferon beta on transcobalamin II-receptor expression and antitumor activity of nitrosylcobalamin. J Natl Cancer Inst 2002; 94 (13): 1010–9.
19. Shimizu N, Hamazoe R, Kanayama H et al. Experimental study of antitumor effect of methyl-B12. Oncology 1987; 44 (3): 169–73.
Авторы
О.А.Громова*1,2, И.Ю.Торшин3,4, О.А.Прокопович4
1 ФГБОУ ВО Ивановская государственная медицинская академия Минздрава России. 153000, Россия, Иваново, Шереметевский пр-т, д. 8;
2 Российский сотрудничающий центр Института микроэлементов под эгидой ЮНЕСКО при ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А;
3 ФГАОУ ВО Московский физико-технический институт (государственный университет) Минобороны России. 141700, Россия, Долгопрудный, Институтский пер., д. 9;
4 ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А
*unesco.gromova@gmail.com
1 ФГБОУ ВО Ивановская государственная медицинская академия Минздрава России. 153000, Россия, Иваново, Шереметевский пр-т, д. 8;
2 Российский сотрудничающий центр Института микроэлементов под эгидой ЮНЕСКО при ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А;
3 ФГАОУ ВО Московский физико-технический институт (государственный университет) Минобороны России. 141700, Россия, Долгопрудный, Институтский пер., д. 9;
4 ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, Островитянова, д. 1А
*unesco.gromova@gmail.com
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O.A.Gromova*1,2, I.Yu.Torshin3,4, O.A.Prokopovich4
1 Ivanovo State Medical Academy of the Ministry of Health of the Russian Federation. 153000, Russian Federation, Ivanovo, Sheremetevskii pr-t, d. 8;
2 Moscow branch of Trace Element Institute for UNESCO at N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1А;
3 Moscow Institute of Physics and Technology. 141700, Russian Federation, Dolgoprudnyi, Institutskii per., d. 9;
4 N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1
*unesco.gromova@gmail.com
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