Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I
文献类型：期刊论文
| 作者 | Xue, Xiang1; Gong, Li-Kun1 ; Maeda, Kazuya2; Luan, Yang1; Qi, Xin-Ming1; Sugiyama, Yuichi2; Ren, Jin1
|
| 刊名 | MOLECULAR PHARMACEUTICS
 |
| 出版日期 | 2011-11 |
| 卷号 | 8期号:6页码:2183-2192 |
| ISSN号 | 1543-8384 |
| 关键词 | organic anion transporter aristolochic acid nephropathy kidney toxicity Oat1 and 3 knockout mice |
| DOI | 10.1021/mp100418u |
| 文献子类 | Article |
| 英文摘要 | Ingestion of atistolochic acid (AA), especially its major constituent aristolochic acid I (AAI), results in severe kidney injury known as aristolochic acid nephropathy (AAN). Although hepatic cytochrome P450s metabolize AAI to reduce its kidney toxicity in mice, the mechanism by which AAI is uptaken by renal cells to induce renal toxicity is largely unknown. In this study, we found that organic anion transporters (OATs) 1 and 3, proteins known to transport drugs from the blood into the tubular epithelium, are responsible for the transportation of AM into renal tubular cells and the subsequent nephrotoincity. AAI uptake in HEK 293 cells stably transfected with human OAT1 or OAT3 was greatly increased compared to that in the control cells, and this uptake was dependent on the AAI concentration. Administration of probenecid, a well-known OAT inhibitor, to the mice reduced AAI renal accumulation and its urinary excretion and protected mice from AM-induced acute tubular necrosis. Further, AAI renal accumulation and severe kidney lesions induced by AAl in Oat1 and OAT3 gene knockout mice all were markedly suppressed compared to those in the wild-type mice. Together, our results suggest that OAT1 and OAT3 have a critical role in AAlrenal accumulation and toxicity. These transporters may serve as a potential therapeutic target against AAN. |
| WOS关键词 | BALKAN ENDEMIC NEPHROPATHY ; CHINESE HERBS NEPHROPATHY ; MOLECULAR-CLONING ; PROTECTS MICE ; RENAL INJURY ; RAT-KIDNEY ; CELLS ; NEPHROTOXICITY ; IDENTIFICATION ; INVOLVEMENT |
| 资助项目 | National Basic Research Program (973 Program)[2006CB504701] ; National Key Technologies RD Program[2009ZX09301-001] ; National Key Technologies RD Program[2008ZX09305-007] ; National Key Technologies RD Program[2009ZX09501-033] ; Nagai Foundation Tokyo[00000000] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000297537300020 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278343]  |
| 专题 | 药物安全性评价中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ren, Jin |
| 作者单位 | 1.Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Univ Tokyo, Lab Mol Pharmacokinet, Grad Sch Pharmaceut Sci, Tokyo, Japan |
| 推荐引用方式 GB/T 7714 | Xue, Xiang,Gong, Li-Kun,Maeda, Kazuya,et al. Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I[J]. MOLECULAR PHARMACEUTICS,2011,8(6):2183-2192. |
| APA | Xue, Xiang.,Gong, Li-Kun.,Maeda, Kazuya.,Luan, Yang.,Qi, Xin-Ming.,...&Ren, Jin.(2011).Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I.MOLECULAR PHARMACEUTICS,8(6),2183-2192. |
| MLA | Xue, Xiang,et al."Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I".MOLECULAR PHARMACEUTICS 8.6(2011):2183-2192. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。