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V101L of human formyl peptide receptor 1 (FPR1) increases receptor affinity and augments the antagonism mediated by cyclosporins | |
2013 | |
发表期刊 | BIOCHEMICAL JOURNAL |
ISSN | 0264-6021 |
EISSN | 1470-8728 |
卷号 | 451页码:245-255 |
发表状态 | 已发表 |
DOI | 10.1042/BJ20121839 |
摘要 | Genetic variation plays a major role in drug response variability. CsA (cyclosporin A), a widely used immunosuppressive agent, is a specific antagonist for FPR1 (formyl peptide receptor 1), which is an important G-protein-coupled chemoattractant receptor in the innate immune system. In order to study the variable responses of cyclosporins to different FPR1 mutants, we investigated the distribution of human FPR1 haplotypes among 209 healthy Han Chinese subjects. The haplotype pattern in Han Chinese were characterized on the basis of five SNPs (single nucleotide polymorphisms), including rs5030878 (p.T11I), rs2070745 (p.V101L), rs5030880 (p.R190W), rs1042229 (p.N192K) and rs867228 (p.A346E). Receptor binding affinity of cyclosporins to FPR1 haplotypes was assessed using N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-FITC in CHO-G(alpha 16) cells stably transfected with cDNAs encoding the top 12 FPR1 haplotypes in the Han Chinese. Variants of FPR1 carrying a single amino, acid substitution of leucine for valine at position 101 (p.Leu(101)) displayed significantly higher pK(i) values for CsA and CsH (cyclosporin H), indicative of an improved receptor affinity. The polymorphism of FPR1 p.Leu(101) also enhanced the inhibitory effects of cyclosporins on fMLF (N-formyl-methionyl-leucyl-phenylalanine)-induced activities, including calcium mobilization, cell chemotaxis and MAPK (mitogen-activated protein kinase) phosphorylation. These results point to a possible complication for clinical use of CsA in patients carrying the p.Leu(101) allele of FPR1. |
关键词 | cyclosporin formyl peptide receptor 1 (FPR1) haplotype pharmacogenomics receptor affinity single nucleotide polymorphism |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Biochemistry & Molecular Biology |
WOS类目 | Biochemistry & Molecular Biology |
WOS记录号 | WOS:000317443500012 |
出版者 | PORTLAND PRESS LTD |
WOS关键词 | SINGLE-NUCLEOTIDE POLYMORPHISMS ; AGGRESSIVE PERIODONTITIS ; CHEMOTACTIC AGONIST ; COMBINATION ; DOXORUBICIN ; INHIBITION ; RESPONSES ; DOMAIN ; ANALOG ; GP41 |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119767 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Wang, Ming-Wei |
作者单位 | 1.Chinese Acad Sci, Natl Ctr Drug Screening, Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Fudan Univ, Inst Genet, Shanghai 200433, Peoples R China 4.Shanghai ADICON Clin Labs, Shanghai 200237, Peoples R China 5.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China |
推荐引用方式 GB/T 7714 | Zhou, Caihong,Zhou, Yan,Wang, Jia,et al. V101L of human formyl peptide receptor 1 (FPR1) increases receptor affinity and augments the antagonism mediated by cyclosporins[J]. BIOCHEMICAL JOURNAL,2013,451:245-255. |
APA | Zhou, Caihong.,Zhou, Yan.,Wang, Jia.,Feng, Yang.,Wang, Haonan.,...&Wang, Ming-Wei.(2013).V101L of human formyl peptide receptor 1 (FPR1) increases receptor affinity and augments the antagonism mediated by cyclosporins.BIOCHEMICAL JOURNAL,451,245-255. |
MLA | Zhou, Caihong,et al."V101L of human formyl peptide receptor 1 (FPR1) increases receptor affinity and augments the antagonism mediated by cyclosporins".BIOCHEMICAL JOURNAL 451(2013):245-255. |
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