三磷酸鸟苷环化水解酶1研究进展
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摘要
三磷酸鸟苷环化水解酶1(GTPCH1)是由GCH1基因编码合成的蛋白产物,在生理条件下,催化底物GTP生成具有生物活性的四氢生物蝶呤(BH4)。BH4是芳香族氨基酸羟化酶的辅酶、一氧化氮合酶的辅因子,参与各种激素和神经递质的合成,并在体内一系列病理生理过程中起重要作用。研究表明,GTPCH1在神经病理性疼痛、多巴反应性肌张力障碍、肿瘤、心血管等疾病的发病机制中起重要作用。本文就GTPCH1在上述疾病发病机制中的作用研究进展进行阐述。
Guanosine triphosphate cyclohydrolase 1( GTPCH1) is a protein encoded by the GCH1 gene,which catalyze GTP to tetrahydrofolinine( BH4) under physiological condition. BH4 is a coenzyme of aromatic amino acid hydroxylase and a cofactor of nitric oxide synthases. BH4 involves in the synthesis of various hormones and neurotransmitters and plays an important role in a series of pathophysiological processes in vivo. Recent studies showed that GTPCH1 is involved in the pathogenesis of neuropathic pain,doparesponsive dystonia,cancer and cardiovascular diseases. In this review,we will discuss the role of GTPCH1 in those diseases mentioned above.
Guanosine triphosphate cyclohydrolase 1( GTPCH1) is a protein encoded by the GCH1 gene,which catalyze GTP to tetrahydrofolinine( BH4) under physiological condition. BH4 is a coenzyme of aromatic amino acid hydroxylase and a cofactor of nitric oxide synthases. BH4 involves in the synthesis of various hormones and neurotransmitters and plays an important role in a series of pathophysiological processes in vivo. Recent studies showed that GTPCH1 is involved in the pathogenesis of neuropathic pain,doparesponsive dystonia,cancer and cardiovascular diseases. In this review,we will discuss the role of GTPCH1 in those diseases mentioned above.
引文
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[25]Belfer I,Dai F,Kehlet H,et al.Association of functional variations in COMT and GCH1 genes with postherniotomy pain and related impairment[J].Pain,2015,156(2):273-279.DOI:10.1097/01.j.pain.0000460307.48701.b0.
[26]梁啸,刘洪美,李庆伟,等.对SNI和CCI两种大鼠神经病理性疼痛模型的实验观察[J].济宁医学院学报,2013,36(1):22-24,27.DOI:10.3969/j.issn.1000-9760.2013.01.005.
[27]Kim SJ,Lee WI,Lee YS,et al.Effective relief of neuropathic pain by adeno-associated virus-mediated expression of a small hairpin RNA against GTP cyclohydrolase 1[J].Mol Pain,2009,5:67.DOI:10.1186/1744-8069-5-67.
[28]Latremoliere A,Costigan M.Combining Human and Rodent Genetics to Identify New Analgesics[J].Neurosci Bull,2018,34(1):143-155.DOI:10.1007/s12264-017-0152-z.
[2]KAUFMAN S,LEVENBERG B.Further studies on the phenylalanine-hydroxylation cofactor[J].J Biol Chem,1959,234:2683-2688.
[3]Kettler R,Bartholini G,Pletscher A.In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin[J].Nature,1974,249(456):476-478.
[4]Sawada M,Sugimoto T,Matsuura S,et al.(6R)-tetrahydrobiopterin increases the activity of tryptophan hydroxylase in rat raphe slices[J].J Neurochem,1986,47(5):1544-1547.DOI:10.1111/j.1471-4159.1986.tb00792.x.
[5]Gorren AC,Mayer B.Tetrahydrobiopterin in nitric oxide synthesis:a novel biological role for pteridines[J].Curr Drug Metab,2002,3(2):133-157.DOI:10.2174/1389200024605154.
[6]Luiking YC,Ten HGA,Wolfe RR,et al.Arginine de novo and nitric oxide production in disease states[J].Am J Physiol Endocrinol Metab,2012,303(10):E1177-E1189.DOI:10.1152/ajpendo.00284.2012.
[7]Oxenkrug GF.Interferon-gamma-inducible kynurenines/pteridines inflammation cascade:implications for aging and aging-associated psychiatric and medical disorders[J].J Neural Transm(Vienna),2011,118(1):75-85.DOI:10.1007/s00702-010-0475-7.
[8]Vásquez-Vivar J.Tetrahydrobiopterin,superoxide,and vascular dysfunction[J].Free Radic Biol Med,2009,47(8):1108-1119.DOI:10.1016/j.freeradbiomed.2009.07.024.
[9]Xue J,Yu C,Sheng W,et al.The Nrf2/GCH1/BH4 Axis Ameliorates Radiation-Induced Skin Injury by Modulating the ROS Cascade[J].J Invest Dermatol,2017,137(10):2059-2068.DOI:10.1016/j.jid.2017.05.019.
[10]Xu Q,Li K,Sun Q,et al.Rare GCH1 heterozygous variants contributing to Parkinson's disease[J].Brain,2017,140(7):e41.DOI:10.1093/brain/awx110.
[11]Tassin J,Dürr A,Bonnet A-M,et al.Levodopa-responsive dystonia:GTP cyclohydrolase I or parkin mutations?[J].Brain,2000,123(6):1112-1121.DOI:10.1093/brain/123.6.1112.
[12]Katus LE,Frucht SJ.An unusual presentation of tyrosine hydroxylase deficiency[J].J Clin Mov Disord,2017,4:18.DOI:10.1186/s40734-017-0065-z.
[13]Crabtree MJ,Channon KM.Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease[J].Nitric Oxide,2011,25(2):81-88.DOI:10.1016/j.niox.2011.04.004.
[14]Wu HE,Baumgardt SL,Fang J,et al.Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy[J].Sci Rep,2016,6:27925.DOI:10.1038/srep27925.
[15]Khoo JP,Zhao L,Alp NJ,et al.Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension[J].Circulation,2005,111(16):2126-2133.DOI:10.1161/01.CIR.0000162470.26840.89.
[16]Liu Y,Baumgardt SL,Fang J,et al.Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling[J].Sci Rep,2017,7(1):3093.DOI:10.1038/s41598-017-03234-6.
[17]Guo YB,He YX,Cui CY,et al.GCH1 plays a role in the highaltitude adaptation of Tibetans[J].Zool Res,2017,38(3):155-162.DOI:10.24272/j.issn.2095-8137.2017.037.
[18]Gacche RN,Meshram RJ.Targeting tumor micro-environment for design and development of novel anti-angiogenic agents arresting tumor growth[J].Prog Biophys Mol Biol,2013,113(2):333-354.DOI:10.1016/j.pbiomolbio.2013.10.001.
[19]Zhu AX,Duda DG,Sahani DV,et al.HCC and angiogenesis:possible targets and future directions[J].Nat Rev Clin Oncol,2011,8(5):292-301.DOI:10.1038/nrclinonc.2011.30.
[20]Ridnour LA,Isenberg JS,Espey MG,et al.Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1[J].Proc Natl Acad Sci U S A,2005,102(37):13147-13152.DOI:10.1073/pnas.0502979102.
[21]代佑果,甘平,李为明,等.四氢生物蝶呤促进肝细胞癌肿瘤血管形成的机制[J].中华肿瘤杂志,2016,38(11):806-811.DOI:10.3760/cma.j.issn.0253-3766.2016.11.002.
[22]Pickert G,Lim HY,Weigert A,et al.Inhibition of GTP cyclohydrolase attenuates tumor growth by reducing angiogenesis and M2-like polarization of tumor associated macrophages[J].Int JCancer,2013,132(3):591-604.DOI:10.1002/ijc.27706.
[23]Young EE,Lariviere WR,Belfer I.Genetic basis of pain variability:recent advances[J].J Med Genet,2012,49(1):1-9.DOI:10.1136/jmedgenet-2011-100386.
[24]李响.基于生物信息技术的慢性疼痛致病基因分析与表达验证[D].中南大学,2013:1-114.
[25]Belfer I,Dai F,Kehlet H,et al.Association of functional variations in COMT and GCH1 genes with postherniotomy pain and related impairment[J].Pain,2015,156(2):273-279.DOI:10.1097/01.j.pain.0000460307.48701.b0.
[26]梁啸,刘洪美,李庆伟,等.对SNI和CCI两种大鼠神经病理性疼痛模型的实验观察[J].济宁医学院学报,2013,36(1):22-24,27.DOI:10.3969/j.issn.1000-9760.2013.01.005.
[27]Kim SJ,Lee WI,Lee YS,et al.Effective relief of neuropathic pain by adeno-associated virus-mediated expression of a small hairpin RNA against GTP cyclohydrolase 1[J].Mol Pain,2009,5:67.DOI:10.1186/1744-8069-5-67.
[28]Latremoliere A,Costigan M.Combining Human and Rodent Genetics to Identify New Analgesics[J].Neurosci Bull,2018,34(1):143-155.DOI:10.1007/s12264-017-0152-z.