nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-43Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESПоложительный контур мочевой кислоты, гомоцистеина, NOX и XOR: нефрологические аспектыРositive loop of uric acid, homocysteine, and NOX and XOR enzymes: implications in nephrologyЗолотухинП. В.ZolotukhinP. V.p.zolotukhin@icloud.comЧмыхалоВ. К.ChmykhaloV. K.p.zolotukhin@icloud.comМакаренкоМ. С.MakarenkoM. S.p.zolotukhin@icloud.comКоринфскаяС. А.KorinfskayaS. A.p.zolotukhin@icloud.comЛебедеваЮ. А.LebedevaU. A.p.zolotukhin@icloud.comКузьминоваО. Н.KuzminovaO. N.p.zolotukhin@icloud.comБелановаА. А.BelanovaA. A.p.zolotukhin@icloud.comГутниковаЛ. В.GutnikovaL. V.p.zolotukhin@icloud.comАлександроваА. А.AleksandrovaA. A.p.zolotukhin@icloud.comАкадемия биологии и биотехнологии Южного федерального университетаRussian Federation2014010920141851622Copyright © Золотухин П.В., Чмыхало В.К., Макаренко М.С., Коринфская С.А., Лебедева Ю.А., Кузьминова О.Н., Беланова А.А., Гутникова Л.В., Александрова А.А., 20142014Золотухин П.В., Чмыхало В.К., Макаренко М.С., Коринфская С.А., Лебедева Ю.А., Кузьминова О.Н., Беланова А.А., Гутникова Л.В., Александрова А.А.Zolotukhin P.V., Chmykhalo V.K., Makarenko M.S., Korinfskaya S.A., Lebedeva U.A., Kuzminova O.N., Belanova A.A., Gutnikova L.V., Aleksandrova A.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.nephrolog.ru/jour/article/view/43

Согласно современным молекулярно-биологическим представлениям, мочевая кислота и гомоцистеин являются активаторами и участниками прооксидантного контура положительных обратных связей, включающего также ксантиноксидоредуктазу и НАДФ∙H-оксидазные комплексы в качестве непосредственных прооксидантных агентов. В силу физиологических и биохимических особенностей почки могут быть одним из наиболее подверженных влиянию этого контура органов. В настоящем обзоре в нефрологическом аспекте представлены биохимические, физиологические и интерактомные эффекты как собственно указанного контура, так и его отдельных компонентов.

According to modern molecular biology concepts, uric acid and homocysteine are activators and participants prooxidant positive feedback loop that also includes xanthine oxidoreductase and NADP∙H-oxidase complexes as direct prooxidant agents. Due to the physiological and biochemical features, the kidney may be the organ that is the most exposed to this contour effects. The present review focuses on nephrological implications of biochemical, physiological and interactomic properties of the circuit and its components.

мочевая кислотагомоцистеинНАДФ∙H-оксидазаксантиноксидоредуктазаконтур положительных обратных связейокислительный стрессгибель клетокпочкамочевая кислотагомоцистеинНАДФ∙H-оксидазаксантиноксидоредуктазаконтур положительных обратных связейокислительный стрессгибель клетокпочкаuric acidhomocysteineNADP∙H oxidasexanthine oxidoreductasepositive feedback loopoxidative stresscell deathkidneyuric acidhomocysteineNADP∙H oxidasexanthine oxidoreductasepositive feedback loopoxidative stresscell deathkidneyReferencesDalton T.P., Shertzer H.G., Puga A. Regulation of gene expression by reactive oxygen. Ann Rev Pharmacol Toxicol 1999; 39: 67-101.Dalton T.P., Shertzer H.G., Puga A. Regulation of gene expression by reactive oxygen. Ann Rev Pharmacol Toxicol 1999; 39: 67-101.Khan N.M., Sandur S.K., Checker R. et al. Pro-oxidants ameliorate radiation-induced apoptosis through activation of the calcium-ERK1/2-Nrf2 pathway. Free Radic Biol Med 2011; 51 (1): 115-128.Khan N.M., Sandur S.K., Checker R. et al. Pro-oxidants ameliorate radiation-induced apoptosis through activation of the calcium-ERK1/2-Nrf2 pathway. Free Radic Biol Med 2011; 51 (1): 115-128.Nam T.G. Lipid peroxidation and its toxicological implications. Toxicol Res 2011; 27 (1): 1-6.Nam T.G. Lipid peroxidation and its toxicological implications. Toxicol Res 2011; 27 (1): 1-6.Zolotukhin P., Kozlova Y., Dovzhik A. et al. Oxidative status interactome map: towards novel approaches in experiment planning, data analysis, diagnostics and therapy. Mol Biosyst 2013; 9 (8): 2085-2096.Zolotukhin P., Kozlova Y., Dovzhik A. et al. Oxidative status interactome map: towards novel approaches in experiment planning, data analysis, diagnostics and therapy. Mol Biosyst 2013; 9 (8): 2085-2096.Золотухин П.В., Александрова А.А., Довжик А.Д. и др. Интерактомика - аналитический инструмент для изучения молекулярных основ нефропатий. Нефрология 2013; (5): 9-15.Золотухин П.В., Александрова А.А., Довжик А.Д. и др. Интерактомика - аналитический инструмент для изучения молекулярных основ нефропатий. Нефрология 2013; (5): 9-15.Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217-246.Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217-246.Uehara S.K., Rosa G. Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr Res 2008; 28 (11): 760-766.Uehara S.K., Rosa G. Association of homocysteinemia with high concentrations of serum insulin and uric acid in Brazilian subjects with metabolic syndrome genotyped for C677T polymorphism in the methylenetetrahydrofolate reductase gene. Nutr Res 2008; 28 (11): 760-766.Bainbridge S.A., von Versen-Höynck F., Roberts J.M. Uric acid inhibits placental system A amino acid uptake. Placenta 2009; 30 (2): 195-200.Bainbridge S.A., von Versen-Höynck F., Roberts J.M. Uric acid inhibits placental system A amino acid uptake. Placenta 2009; 30 (2): 195-200.Bainbridge S.A., Deng J.S., Roberts J.M. Increased xanthine oxidase in the skin of preeclamptic women. Reprod Sci 2009; 16(5): 468-478.Bainbridge S.A., Deng J.S., Roberts J.M. Increased xanthine oxidase in the skin of preeclamptic women. Reprod Sci 2009; 16(5): 468-478.Sipkens J.A., Hahn N.E., Blom H.J. et al. S-Adenosylhomo-cysteine induces apoptosis and phosphatidylserine exposure in endothelial cells independent of homocysteine. Atherosclerosis 2012; 221 (1): 48-54.Sipkens J.A., Hahn N.E., Blom H.J. et al. S-Adenosylhomo-cysteine induces apoptosis and phosphatidylserine exposure in endothelial cells independent of homocysteine. Atherosclerosis 2012; 221 (1): 48-54.Zhang C., Yi F., Xia M. et al. NMDA receptor-mediated activation of NADPH oxidase and glomerulosclerosis in hyperhomocysteinemic rats. Antioxid Redox Signal 2010; 13 (7): 975-986.Zhang C., Yi F., Xia M. et al. NMDA receptor-mediated activation of NADPH oxidase and glomerulosclerosis in hyperhomocysteinemic rats. Antioxid Redox Signal 2010; 13 (7): 975-986.Glantzounis G.K., Tsimoyiannis E.C., Kappas A.M., Galaris D.A. Uric acid and oxidative stress. CurrPharm Des 2005; 11 (32): 45-51.Glantzounis G.K., Tsimoyiannis E.C., Kappas A.M., Galaris D.A. Uric acid and oxidative stress. CurrPharm Des 2005; 11 (32): 45-51.Maples K.R., Mason R.P. Free radical metabolite of uric acid. J Biol Chem 1988; 263 (4): 1709-1712.Maples K.R., Mason R.P. Free radical metabolite of uric acid. J Biol Chem 1988; 263 (4): 1709-1712.Cervellati C., Romani A., Seripa D. et al. Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer’s Disease or Vascular Dementia. J Neurol Sci 2014; 337 (1-2): 156-161.Cervellati C., Romani A., Seripa D. et al. Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer’s Disease or Vascular Dementia. J Neurol Sci 2014; 337 (1-2): 156-161.Sautin Y.Y., Nakagawa T., Zharikov S., Johnson R.J. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 2007; 293 (2): 584-596.Sautin Y.Y., Nakagawa T., Zharikov S., Johnson R.J. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol Cell Physiol 2007; 293 (2): 584-596.Cave A.C., Brewer A.C., Narayanapanicker A. et al. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 2006; 8 (5-6): 691-728.Cave A.C., Brewer A.C., Narayanapanicker A. et al. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 2006; 8 (5-6): 691-728.Deng B., Xie S., Wang J. et al. Inhibition of protein kinase C β(2) prevents tumor necrosis factor-α-induced apoptosis and oxidative stress in endothelial cells: the role of NADPH oxidase subunits. J Vasc Res 2012; 49 (2): 144-159.Deng B., Xie S., Wang J. et al. Inhibition of protein kinase C β(2) prevents tumor necrosis factor-α-induced apoptosis and oxidative stress in endothelial cells: the role of NADPH oxidase subunits. J Vasc Res 2012; 49 (2): 144-159.Bolander-Gouaille C. Homocysteine Related Vitamins and Neuropsychiatric Disorders. Springer-Verlag, Paris, 2007; 150-212.Bolander-Gouaille C. Homocysteine Related Vitamins and Neuropsychiatric Disorders. Springer-Verlag, Paris, 2007; 150-212.Jakubowski H. Homocysteine Thiolactone: Metabolic Origin and Protein Homocysteinylation in Humans. Journal of Nutrition 2000; 130: 377-381.Jakubowski H. Homocysteine Thiolactone: Metabolic Origin and Protein Homocysteinylation in Humans. Journal of Nutrition 2000; 130: 377-381.Vitvitsky V., Mosharov E., Tritt M. et al. Redox regulation of homocysteine-dependent glutathione synthesis. Redox Rep 2003; 8 (1): 57-63.Vitvitsky V., Mosharov E., Tritt M. et al. Redox regulation of homocysteine-dependent glutathione synthesis. Redox Rep 2003; 8 (1): 57-63.Abraham J., Cho L. The homocysteine hypothesis: Still relevant to the prevention and treatment of cardiovascular disease? Cleveland Clinic Journal of Medicine 2010; 77: 911-918.Abraham J., Cho L. The homocysteine hypothesis: Still relevant to the prevention and treatment of cardiovascular disease? Cleveland Clinic Journal of Medicine 2010; 77: 911-918.Вайнер А.С., Жечев Д.А., Кечин А.А. и др. Метаболизм фолатов и врожденные аномалии развития. Мать и Дитя в Кузбассе 2011; (45): 3-11.Вайнер А.С., Жечев Д.А., Кечин А.А. и др. Метаболизм фолатов и врожденные аномалии развития. Мать и Дитя в Кузбассе 2011; (45): 3-11.Schalinske K., Smazal A. Homocysteine Imbalance: a Pathological Metabolic Marker. Advances in Nutrition 2012; 3; 755-762.Schalinske K., Smazal A. Homocysteine Imbalance: a Pathological Metabolic Marker. Advances in Nutrition 2012; 3; 755-762.Kinoshita M., Numata S., Tajima A. et al. Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics 2013; 5: 84-90.Kinoshita M., Numata S., Tajima A. et al. Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics 2013; 5: 84-90.Mosharov E., Cranford M.R., Banerjee R. The quantatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulphuration pathway and its regulation by redox changes. Biochemistry 2000; 39: 13005-13011.Mosharov E., Cranford M.R., Banerjee R. The quantatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulphuration pathway and its regulation by redox changes. Biochemistry 2000; 39: 13005-13011.Bostom A.G., Shemin D., Lapane K.L. et al. Hyperhomocysteinemia and traditional cardiovascular disease risk factors in endstage renal disease patients on dialysis: a case-control study. Atherosclerosis 1995; 114 (1): 93-103.Bostom A.G., Shemin D., Lapane K.L. et al. Hyperhomocysteinemia and traditional cardiovascular disease risk factors in endstage renal disease patients on dialysis: a case-control study. Atherosclerosis 1995; 114 (1): 93-103.van Guldener C., Donker A.J., Jakobs C. et al. No net renal extraction of homocysteine in fasting humans. Kidney Int 1998; 54: 166-169van Guldener C., Donker A.J., Jakobs C. et al. No net renal extraction of homocysteine in fasting humans. Kidney Int 1998; 54: 166-169Refsum H., Guttormsen A.B., Fiskerstrand T., Ueland P.M. Hyperhomocysteinemia in terms of steady state kinetics. Eur J Pediatrics 1998; 157: 45-49.Refsum H., Guttormsen A.B., Fiskerstrand T., Ueland P.M. Hyperhomocysteinemia in terms of steady state kinetics. Eur J Pediatrics 1998; 157: 45-49.Guttormsen A.B., Ueland P.M., Svarstad E., Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52 (2): 495-502.Guttormsen A.B., Ueland P.M., Svarstad E., Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52 (2): 495-502.Williams K.T., Schalinske K.L. New insights into the regulation of methyl group and homocysteine metabolism. J Nutr 2007; 137 (2): 311-314.Williams K.T., Schalinske K.L. New insights into the regulation of methyl group and homocysteine metabolism. J Nutr 2007; 137 (2): 311-314.Blom H.J., Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis 2011; 34 (1): 75-81Blom H.J., Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis 2011; 34 (1): 75-81Chen N.C., Yang F., Capecci L.M. et al. Regulation of homocysteine metabolism and methylation in human and mouse tissues. FASEB J 2010; 24: 2804-2817.Chen N.C., Yang F., Capecci L.M. et al. Regulation of homocysteine metabolism and methylation in human and mouse tissues. FASEB J 2010; 24: 2804-2817.Bao X.M., Wu C.F., Lu G.P. Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK. Atherosclerosis 2010; 210 (1): 114-121.Bao X.M., Wu C.F., Lu G.P. Atorvastatin inhibits homocysteine-induced oxidative stress and apoptosis in endothelial progenitor cells involving Nox4 and p38MAPK. Atherosclerosis 2010; 210 (1): 114-121.Motti C., Gnasso A., Bernardini S. et al. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease. Atherosclerosis 1998; 139 (2): 377-383.Motti C., Gnasso A., Bernardini S. et al. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease. Atherosclerosis 1998; 139 (2): 377-383.Ozkan Y., Yardim-Akaydin S., Imren E. et al. Increased plasma homocysteine and allantoin levels in coronary artery disease: possible link between homocysteine and uric acid oxidation. Acta Cardiol 2006; 61 (4): 432-439.Ozkan Y., Yardim-Akaydin S., Imren E. et al. Increased plasma homocysteine and allantoin levels in coronary artery disease: possible link between homocysteine and uric acid oxidation. Acta Cardiol 2006; 61 (4): 432-439.Ueno N., Takeya R., Miyano K. et al. The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem 2005; 280 (24): 23328-23339.Ueno N., Takeya R., Miyano K. et al. The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem 2005; 280 (24): 23328-23339.Cairns B., Kim J.Y., Tang X.N., Yenari M.A. NOX inhibitors as a therapeutic strategy for stroke and neurodegenerative disease. Curr Drug Targets 2012; 13 (2): 199-206.Cairns B., Kim J.Y., Tang X.N., Yenari M.A. NOX inhibitors as a therapeutic strategy for stroke and neurodegenerative disease. Curr Drug Targets 2012; 13 (2): 199-206.Vignais P.V. The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 2002; 59 (9): 1428-1459.Vignais P.V. The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 2002; 59 (9): 1428-1459.Bánfi B., Molnár G., Maturana A. et al. A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem 2001; 276 (40): 37594-37601.Bánfi B., Molnár G., Maturana A. et al. A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem 2001; 276 (40): 37594-37601.Martyn K.D., Frederick L.M., von Loehneysen K. et al. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 2006; 18 (1): 69-82.Martyn K.D., Frederick L.M., von Loehneysen K. et al. Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 2006; 18 (1): 69-82.Manea A., Manea S.A., Gafencu A.V. et al. AP-1-dependent transcriptional regulation of NADPH oxidase in human aortic smooth muscle cells: role of p22phox subunit. Arterioscler Thromb Vasc Biol 2008; 28 (5): 878-885.Manea A., Manea S.A., Gafencu A.V. et al. AP-1-dependent transcriptional regulation of NADPH oxidase in human aortic smooth muscle cells: role of p22phox subunit. Arterioscler Thromb Vasc Biol 2008; 28 (5): 878-885.Pendyala S., Moitra J., Kalari S. et al. Nrf2 regulates hyperoxia-induced Nox4 expression in human lung endothelium: identification of functional antioxidant response elements on the Nox4 promoter. Free Radic Biol Med 2011; 50 (12): 1749-1759.Pendyala S., Moitra J., Kalari S. et al. Nrf2 regulates hyperoxia-induced Nox4 expression in human lung endothelium: identification of functional antioxidant response elements on the Nox4 promoter. Free Radic Biol Med 2011; 50 (12): 1749-1759.Jin D.Y., Chae H.Z., Rhee S.G., Jeang K.T. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem 1997; 272 (49): 30952-30961.Jin D.Y., Chae H.Z., Rhee S.G., Jeang K.T. Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J Biol Chem 1997; 272 (49): 30952-30961.Sun Y., Oberley L.W. Redox regulation of transcriptional activators. Free Radic Biol Med 1996; 21 (3): 335-348.Sun Y., Oberley L.W. Redox regulation of transcriptional activators. Free Radic Biol Med 1996; 21 (3): 335-348.Turpaev K.T. Keap1-Nrf2 signaling pathway: mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles. Biochemistry (Mosc) 2013; 78. (2): 111-126.Turpaev K.T. Keap1-Nrf2 signaling pathway: mechanisms of regulation and role in protection of cells against toxicity caused by xenobiotics and electrophiles. Biochemistry (Mosc) 2013; 78. (2): 111-126.Hirota K., Murata M., Sachi Y. et al. Distinct roles of thiore-doxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB. J Biol Chem 1999; 274 (39): 27891-27897.Hirota K., Murata M., Sachi Y. et al. Distinct roles of thiore-doxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB. J Biol Chem 1999; 274 (39): 27891-27897.Sipkens J.A., Hahn N., van den Brand C.S. et al. Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity. Cell Biochem Biophys 2013; 67 (2): 341-352.Sipkens J.A., Hahn N., van den Brand C.S. et al. Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity. Cell Biochem Biophys 2013; 67 (2): 341-352.Kim Y.C., Yamaguchi Y., Kondo N. et al. Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response. Oncogene 2003; 22 (12): 1860-1865Kim Y.C., Yamaguchi Y., Kondo N. et al. Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response. Oncogene 2003; 22 (12): 1860-1865Iwasaki K., Mackenzie E.L., Hailemariam K. et al. Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H. gene and role of Ref-1 during erythroid differentiation of K562 cells. Mol Cell Biol 2006; 26 (7): 2845-2856.Iwasaki K., Mackenzie E.L., Hailemariam K. et al. Hemin-mediated regulation of an antioxidant-responsive element of the human ferritin H. gene and role of Ref-1 during erythroid differentiation of K562 cells. Mol Cell Biol 2006; 26 (7): 2845-2856.Hirota K., Matsui M., Iwata S. et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci USA 1997; 94 (8): 3633-3638.Hirota K., Matsui M., Iwata S. et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci USA 1997; 94 (8): 3633-3638.Yu M., Li H., Liu Q. et al. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell Signal 2011; 23 (5): 883-892.Yu M., Li H., Liu Q. et al. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell Signal 2011; 23 (5): 883-892.Reichard J.F., Motz G.T., Puga A. Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res 2007; 35 (21): 7074-7086.Reichard J.F., Motz G.T., Puga A. Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res 2007; 35 (21): 7074-7086.Arnér E.S., Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000; 267 (20): 6102-6109.Arnér E.S., Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000; 267 (20): 6102-6109.UniProt [электронный ресурс]: www.uniprot.org (Дата обращения - 7 апреля 2014).UniProt [электронный ресурс]: www.uniprot.org (Дата обращения - 7 апреля 2014).Lipkowitz M.S. Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep 2012; 14 (2): 179-188.Lipkowitz M.S. Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep 2012; 14 (2): 179-188.Lee V.W., Wang Y.M., Wang Y.P. et al. Regulatory immune cells in kidney disease. Am J Physiol Renal Physiol 2008; 295 (2): F335-F342.Lee V.W., Wang Y.M., Wang Y.P. et al. Regulatory immune cells in kidney disease. Am J Physiol Renal Physiol 2008; 295 (2): F335-F342.

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