Nucleosides, Nucleotides and Nucleic Acids最新文献_第3页

A review of the implication of hypoxanthine excess in the physiopathology of Lesch–Nyhan disease 次黄嘌呤过量在Lesch-Nyhan病生理病理中的意义综述

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1147579

R. Torres, C. Prior, M. G. García, J. Puig

引用次数: 12

Prevalence of URAT1 allelic variants in the Roma population 罗马人群中URAT1等位基因变异的患病率

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1168839

B. Stibůrková, D. Gabriková, P. Čepek, P. Šimek, P. Kristian, E. Córdoba-Lanús, F. Claverie-Martín

{"title":"Prevalence of URAT1 allelic variants in the Roma population","authors":"B. Stibůrková, D. Gabriková, P. Čepek, P. Šimek, P. Kristian, E. Córdoba-Lanús, F. Claverie-Martín","doi":"10.1080/15257770.2016.1168839","DOIUrl":"https://doi.org/10.1080/15257770.2016.1168839","url":null,"abstract":"ABSTRACT The Roma represents a transnational ethnic group, with a current European population of 8–10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians. However, RHUC 1 patients have been described in a variety of ethnic groups (e.g., Arab Israelis, Iraqi Jews, Caucasians, and Roma) and in geographically noncontiguous countries. This study confirms our previous findings regarding the high frequency of SLC22A12 variants observed. Frequencies of the c.1245_1253del and c.1400C>T variants were found to be 1.92% and 5.56%, respectively, in a subgroup of the Roma population from five regions in three countries: Slovakia, Czech Republic, and Spain. Our findings suggested that the common dysfunction allelic variants of URAT1 exist in the general Roma population and thus renal hypouricemia should be kept in differential diagnostic algorithm on Roma patients with defect in renal tubular urate transport. This leads to confirm that the genetic drift in the Roma have increased the prevalence of hereditary disorders caused by very rare variants in major population.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"51 1","pages":"529 - 535"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74569844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Purification, activity, and expression levels of two uridine-cytidine kinase isoforms in neuroblastoma cell lines 两种尿苷-胞苷激酶亚型在神经母细胞瘤细胞系中的纯化、活性和表达水平

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2015.1124998

R. Meinsma, A. V. van Kuilenburg

引用次数: 8

Stably transfected adherent cancer cell models with decreased expression of 5′-nucleotidase cN-II 稳定转染5′-核苷酸酶cN-II表达降低的粘附癌细胞模型

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1163375

G. Bricard, Emeline Cros-Perrial, C. Machon, C. Dumontet, L. Jordheim

引用次数: 8

Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury Urat1-Uox双敲除小鼠是肾性低尿酸血症和运动性急性肾损伤的实验动物模型

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1143559

M. Hosoyamada, Yu Tsurumi, Hidenori Hirano, N. H. Tomioka, Y. Sekine, T. Morisaki, S. Uchida

{"title":"Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury","authors":"M. Hosoyamada, Yu Tsurumi, Hidenori Hirano, N. H. Tomioka, Y. Sekine, T. Morisaki, S. Uchida","doi":"10.1080/15257770.2016.1143559","DOIUrl":"https://doi.org/10.1080/15257770.2016.1143559","url":null,"abstract":"ABSTRACT Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI). Mice were given a variable content of allopurinol for one week followed by HPLC measurement of urate and creatinine concentrations in spot urine and blood from the tail. The urinary excretion of urate in Urat1-Uox-DKO mice was approximately 25 times higher than those of humans. With allopurinol, the plasma urate levels of Urat1-Uox-DKO mice were lower than those of Uox-KO mice. There were no differences in the urinary urate excretions between Urat1-Uox-DKO and Uox-KO mice administered with 9 mg allopurinol /100 g feed. In the absence of allopurinol, plasma creatinine levels of some Urat1-Uox-DKO mice were higher than those of Uox-KO mice. Consequently, hypouricemia and normouricosuria may indicate that the Urat1-Uox-DKO mouse administered with allopurinol may represent a suitable animal model of RHUC type 1. Urat1-Uox-DKO mice without allopurinol exhibited acute kidney injury, thus providing additional benefit as a potential animal model for EIAKI. Finally, our data indicate that allopurinol appears to provide prophylactic effects for EIAKI.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"79 1","pages":"543 - 549"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83320371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Role of genomic factors beyond thymidylate synthase in the prediction of response to 5-fluorouracil 胸苷酸合成酶以外的基因组因素在预测5-氟尿嘧啶反应中的作用

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1218020

G. Peters, K. Smid, E. Meijer, C. V. van Groeningen, L. Leon

{"title":"Role of genomic factors beyond thymidylate synthase in the prediction of response to 5-fluorouracil","authors":"G. Peters, K. Smid, E. Meijer, C. V. van Groeningen, L. Leon","doi":"10.1080/15257770.2016.1218020","DOIUrl":"https://doi.org/10.1080/15257770.2016.1218020","url":null,"abstract":"ABSTRACT 5-Fluorouracil (5FU) is still a major drug in combinations regimens for the treatment of colorectal cancer (CRC) both in the adjuvant and palliative setting. 5FU or its oral prodrug capecitabine is usually combined with irinotecan/oxaliplatin and the novel agents bevacizumab/cetuximab. Although this improved the outcome, the overall prognosis in patients with metastasized disease is still relatively poor. Although the target for 5FU, thymidylate synthase was shown to have a predictive value, this could only predict response in a subset of patients. Given the heterogeneous and complex nature of CRC, it is likely that other aberrations can affect therapeutic response. As an alternative, we investigated Copy number alterations using oligonucleotide-based high-throughput array-comparative-genomic-hybridization (aCGH) to obtain an unbiased screening of the whole genetic spectrum. Chromosomal aberrations have been identified in 85% of CRC patients and include genomic regions harboring copy number alterations in the DNA. These alterations may change the expression of many genes and might explain the differential response to therapy as shown in recent studies with several 5FU combinations. In order to clarify new predictive parameters for 5FU, we used aCGH in a historical cohort of patients, which received treatment with single agent 5FU, and an unsupervised clustering analysis showed a statistical (p < 0.05) difference between responding and nonresponding patients. We also find that several regions showed differences between responders/non-responders, such as losses in 12p12.3–12q15 and in 18p (where TS is located) in responding patients. Genome-wide analysis may provide an additional tool to discriminate between responders and nonresponders.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"14 1","pages":"595 - 603"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72861585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Orotate (orotic acid): An essential and versatile molecule 乳香酸:一种重要的多用途分子

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1147580

M. Löffler, E. Carrey, E. Zameitat

{"title":"Orotate (orotic acid): An essential and versatile molecule","authors":"M. Löffler, E. Carrey, E. Zameitat","doi":"10.1080/15257770.2016.1147580","DOIUrl":"https://doi.org/10.1080/15257770.2016.1147580","url":null,"abstract":"ABSTRACT Orotate (OA) is well-known as a precursor in biosynthesis of pyrimidines; in mammals it is released from the mitochondrial dihydroorotate dehydrogenase (DHODH) for conversion to UMP by the cytoplasmic UMP synthase enzyme. OA is also a normal part of the diet, being found in milk and dairy products, and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes. Early research into nutrition identified orotate as “vitamin B13,” and its use as a complex with organic cations or metal ions was promulgated in body-building, and in assisting therapies of metabolic syndromes. It has recently been established that the amelioration of gout by dairy products arises from the competition of orotate and urate at the hURAT1 transporter. The orotic aciduria that arises in children with defective UMP synthase can be rescued by oral uridine therapy, since UMP is the end-product and also a feedback inhibitor of the de novo pathway. In contrast, Miller (dysmorphology) syndrome is connected with defects in DHODH, and hence in the supply of OA, and cannot be helped by uridine. Other models of dysmorphisms are connected with enzymes early in the pyrimidine de novo pathway. We conclude that the OA molecule is itself required for the regulation of genes that are important in the development of cells, tissues and organisms.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"76 1","pages":"566 - 577"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83852039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 48

Ultrasonography in the diagnosis of asymptomatic hyperuricemia and gout 超声检查在无症状高尿酸血症和痛风诊断中的价值

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2015.1124999

J. Puig, L. Beltrán, C. Mejia-Chew, D. Tevar, R. Torres

引用次数: 14

Advances in purine and pyrimidine metabolism in health and diseases 嘌呤和嘧啶代谢在健康和疾病中的研究进展

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2016.1218022

M. Hirano, G. Peters

引用次数: 10

Mitochondrial purine and pyrimidine metabolism and beyond 线粒体嘌呤和嘧啶代谢及其他

Nucleosides, Nucleotides and Nucleic Acids Pub Date : 2016-12-01 DOI: 10.1080/15257770.2015.1125001

Liya Wang

{"title":"Mitochondrial purine and pyrimidine metabolism and beyond","authors":"Liya Wang","doi":"10.1080/15257770.2015.1125001","DOIUrl":"https://doi.org/10.1080/15257770.2015.1125001","url":null,"abstract":"ABSTRACT Carefully balanced deoxynucleoside triphosphate (dNTP) pools are essential for both nuclear and mitochondrial genome replication and repair. Two synthetic pathways operate in cells to produce dNTPs, e.g., the de novo and the salvage pathways. The key regulatory enzymes for de novo synthesis are ribonucleotide reductase (RNR) and thymidylate synthase (TS), and this process is considered to be cytosolic. The salvage pathway operates both in the cytosol (TK1 and dCK) and the mitochondria (TK2 and dGK). Mitochondrial dNTP pools are separated from the cytosolic ones owing to the double membrane structure of the mitochondria, and are formed by the salvage enzymes TK2 and dGK together with NMPKs and NDPK in postmitotic tissues, while in proliferating cells the mitochondrial dNTPs are mainly imported from the cytosol produced by the cytosolic pathways. Imbalanced mitochondrial dNTP pools lead to mtDNA depletion and/or deletions resulting in serious mitochondrial diseases. The mtDNA depletion syndrome is caused by deficiencies not only in enzymes in dNTP synthesis (TK2, dGK, p53R2, and TP) and mtDNA replication (mtDNA polymerase and twinkle helicase), but also in enzymes in other metabolic pathways such as SUCLA2 and SUCLG1, ABAT and MPV17. Basic questions are why defects in these enzymes affect dNTP synthesis and how important is mitochondrial nucleotide synthesis in the whole cell/organism perspective? This review will focus on recent studies on purine and pyrimidine metabolism, which have revealed several important links that connect mitochondrial nucleotide metabolism with amino acids, glucose, and fatty acid metabolism.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"213 1","pages":"578 - 594"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79483297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 64