尿酸转运蛋白研究进展

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (11): 1289-1294.

尿酸转运蛋白研究进展

朱立然, 陈光亮

安徽中医学院中西医结合临床学院,合肥 230038,安徽

收稿日期:2012-06-29 修回日期:2012-08-22 发布日期:2012-12-04
通讯作者: 陈光亮,通信作者,男,博士,教授,研究方向:内分泌代谢药理。E-mail: chguangl@163.com
作者简介:朱立然,女,硕士研究生,研究方向:内分泌代谢药理。E-mail: liranzhu2009@yahoo.cn
基金资助:
国家自然科学基金资助项目(81073112)

Progress in uric acid transporters

ZHU Li-ran, CHEN Guang-liang

Integrative Medicine College,Anhui University of Traditional Chinese, Hefei 230038, Anhui, China

Received:2012-06-29 Revised:2012-08-22 Published:2012-12-04

摘要/Abstract

摘要： 体内尿酸经肾脏转运时需依赖肾小管上皮细胞上的转运蛋白。现已明确有4种尿酸盐转运蛋白参与了人近曲肾小管对尿酸盐的转运:即负责尿酸重吸收的尿酸盐阴离子转运体1(hURAT1),及负责尿酸分泌的尿酸盐转运体(UAT)和有机阴离子转运体(OAT1和OAT3)。最近,又发现了一种负责将尿酸分泌到细胞外,参与肾脏近曲小管对尿酸盐的重吸收的转运蛋白--葡萄糖转运蛋白9(GLUT9)。本文对尿酸转运蛋白的特点、功能及调节机制进行综述。

关键词: 高尿酸血症, 尿酸转运蛋白, 进展

Abstract: Transport of uric acid by the kidneys rely on the transport protein in the renal tubular epithelial cells. Four kinds of urate transporters are involved in proximal tubular urate transport: human urate-anion exchanger 1(hURAT1) , which is responsible for the reabsorption of urate, human urate transporter (UAT) and organic anion transporter (OAT1 and OAT3),there are responsible for uric acid secretion. Recently, also found that the one responsible for uric acid secretion into the extracellular, involved in the renal proximal tubule reabsorption of urate transporter protein - glucose transporter protein (GLUT9). This article summarized the features, functions and regulatory mechanisms of uric acid transport protein.

Key words: Hyperuricemia, Uric acid transporters, Progress

中图分类号:

R589

朱立然, 陈光亮. 尿酸转运蛋白研究进展[J]. 中国临床药理学与治疗学, 2012, 17(11): 1289-1294.

ZHU Li-ran, CHEN Guang-liang. Progress in uric acid transporters[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(11): 1289-1294.

参考文献

[1] Chang HY, Tung CW, Lee PH, et al.Hyperuricemia as an independent risk factor of chronic kidney disease in middle-aged and elderly population[J].Am J Med Sci, 2010, 339(6):509-515.
[2] Richette P, Bardin T.Gout[J].Lancet, 2010, 375(9711): 318-328.
[3] Duan P, You G.Short-term regulation of organic anion transporters[J]. Pharmacol Ther, 2010,125(1): 55-61.
[4] Enomoto A, Kimura H, Chairoungdua A, et al.Molecular identification of a renal urate anion exchanger that regulates blood urate levels[J]. Nature, 2002,417(6887):447-452.
[5] Hosoyamada M, Ichida K, Enomoto A, et al.Function and localization of urate transporter 1 in mouse kidney[J]. J Am Soc Nephrol, 2004,15(2):261-268.
[6] Uetake D, Ohno I, Ichida K, et al.Effect of fenofibrate on uric acid metabolism and urate transporter 1[J]. Intern Med, 2010,49(2):89-94.
[7] Hu QH, Jiao RQ, Wang X, et al.Simiao pill ameliorates urate underexcretion and renal dysfunction in hyperuricemic mice[J]. J Ethnopharmacol, 2010,128(3):685-692.
[8] Takahashi T, Tsuchida S, Oyamada T, et al.Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese[J]. Pediatr Nephrol, 2005,20(5):576-578.
[9] Ichida K, Hosoyamada M, Kamatani N, et al.Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese[J].Clin Genet, 2008,74(3):243-251.
[10] Graessler J, Graessler A, Unger S, et al.Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population[J].Arthritis Rheum, 2006,54(1):292-300.
[11] Guan M, Zhang J, Chen Y, et al.High-resolution melting analysis for the rapid detection of an intronic single nucleotide polymorphism in SLC22A12 in male patients with primary gout in China[J]. Scand J Rheumatol, 2009,38(4):276-281.
[12] Hamada T, Ichida K, Hosoyamada M, et al.Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients[J]. Am J Hypertens, 2008,21(10):1157-1162.
[13] Yu Z, Fong WP, Cheng CH.Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) expressed in human embryonic kidney cells[J]. Drug Metab Dispos, 2007,35(6):981-986.
[14] Lasko B, Sheedy B, Hingorani V, et al.RDEA594, a novel uricosuric agent, significantly reduced serum urate levels and was well tolerated in a phase 2 a pilot study in hyeruricemic gout patients[J]. Arthritis Rheum, 2009, 60: 413-414.
[15] Leal-Pinto E, Cohen BE, Lipkowitz MS, et al.Functional analysis and molecular model of the human urate transporter/channel, hUAT[J]. Am J Physiol Renal Physiol, 2002, 283(1):F150-163.
[16] Lipkowitz MS, Leal-Pinto E, Cohen BE, et al.Galectin 9 is the sugar-regulated urate transporter/channel UAT[J]. Glycoconj J,2004,19(7/8/9):491-498.
[17] Jutabha P, Anzai N, Ichida K,et al.Functional characterization of a novel urate efflux transporter URATv1 (SLC2A9) and its relation to renal hypouricemia[J]. FASEB J, 2009, 23: 603.
[18] Anzai N, Ichida K, Jutabha P.Plasma urate level is directly regulated by a voltage-driven urate efflux transport URATv1(SLC2A9) in humans[J]. J Biol Chem, 2008,283(40):26834-26838.
[19] Le MT, Shafiu M, Mu W, et al.SLC2A9--a fructose transporter identified as a novel uric acid transporter[J]. Nephrol Dial Transplant, 2008,23(9):2746-2749.
[20] Matsuo H, Chiba T, Nagamori S, et al.Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia[J]. Am J Hum Genet, 2008,83(6):744-751.
[21] Dinour D, Gray NK, Campbell S, et al.Homozygous SLC2A9 mutations cause severe renal hypouricemia[J]. J Am Soc Nephrol, 2010,21(1):64-72.
[22] Preitner F, Bonny O, Laverrière A, et al.Glut9 is a major regulator ofurate homeostasis and its genetic inactivation induces hyperuricosuria andurate nephropathy[J]. Proc Natl Acad Sci USA, 2009,106(36):15501-15506.
[23] Ichida K, Hosoyamada M, Kimura H, et al.Urate transport via human PAH transporter hOAT1 and its gene structure[J]. Kidney Int, 2003,63(1):143-155.
[24] Uwai Y, Ida H, Tsuji Y, et al.Renal transport of adefovir, cidofovir, and tenofovir by SLC22A family members (hOAT1, hOAT3, and hOCT2)[J]. Pharm Res, 2007,24(4):811-815.
[25] Sato M, Mamada H, Anzai N, et al.Renal secretion of uric acid by organic anion transporter 2 (OAT2/SLC22A7) in human[J]. Biol Pharm Bull, 2010,33(3):498-503.
[26] Perry JL, Dembla-Rajpal N, Hall LA, et al.A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport[J]. J Biol Chem, 2006,281(49):38071-38079.
[27] Mizuno N, Takahashi T, Iwase Y, et al.Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate[J]. Drug Metab Dispos, 2007,35(8):1429-1434.
[28] Bahn A, Hagos Y, Reuter S,et al.Identification of a new urate and high affinity nicotinate transporter, hOAT10 (SLC22A13)[J]. J Biol Chem, 2008,283(24):16332-16341.
[29] Dalbeth N, Merriman T.Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout[J].Rheumatology (Oxford), 2009,48(3):222-226.