The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel
文献类型：期刊论文
| 作者 | Li, Ping2; Zhu, Jin3; Kong, Qingya3; Jiang, Baifeng3; Wan, Xia2,4; Yue, Jinfeng2; Li, Min1,2,6; Jiang, Hualiang3,5 ; Li, Jian3; Gao, Zhaobing2
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| 刊名 | TOXICOLOGY LETTERS
 |
| 出版日期 | 2013-06-07 |
| 卷号 | 219期号:3页码:211-217 |
| 关键词 | Mancozeb Fungicide KCNQ2 channel Ethylene bis-dithiocarbamates |
| ISSN号 | 0378-4274 |
| DOI | 10.1016/j.toxlet.2013.03.020 |
| 文献子类 | Article |
| 英文摘要 | Mancozeb (manganese/ zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration. In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity. Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0.92 perpendicular to 0.23 mu M. Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects. In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion. However, the iron (Fe3+) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components. Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system. (C) 2013 Elsevier Ireland Ltd. All rights reserved. |
| WOS关键词 | CYSTEINE-MODIFYING REAGENT ; PARKINSONS-DISEASE ; K+ CHANNELS ; EZOGABINE RETIGABINE ; AGRICULTURAL HEALTH ; MOUSE-BRAIN ; EXPOSURE ; MANEB ; PESTICIDES ; PARAQUAT |
| 资助项目 | National Key Basic Research Program of China[2013CB910604] ; National Science and Technology Major Project on "Key New Drug Creation and Manufacturing Program"[2013ZX09103001-016] ; National Natural Science Foundation of China (NSFC)[81072579] ; National Natural Science Foundation of China (NSFC)[21222211] ; Program for New Century Excellent Talents in University[NCET-12-0853] ; Shanghai Committee of Science and Technology[11DZ2260600] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000318971900002 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277587]  |
| 专题 | 神经药理学研究国际科学家工作站 中科院受体结构与功能重点实验室 成果转移转化处 新药研究国家重点实验室 |
| 通讯作者 | Li, Jian |
| 作者单位 | 1.Johns Hopkins Univ, High Throughput Biol Ctr, Dept Neurosci, Baltimore, MD 21205 USA; 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 4.Chongqing Med Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Chongqing 400016, Peoples R China; 5.Chinese Acad Sci, State Key Lab Drug Res, Inst Mat Med, Shanghai 201203, Peoples R China; 6.Johns Hopkins Univ, Sch Med, Johns Hopkins Ion Channel Ctr, Baltimore, MD 21205 USA |
| 推荐引用方式 GB/T 7714 | Li, Ping,Zhu, Jin,Kong, Qingya,et al. The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel[J]. TOXICOLOGY LETTERS,2013,219(3):211-217. |
| APA | Li, Ping.,Zhu, Jin.,Kong, Qingya.,Jiang, Baifeng.,Wan, Xia.,...&Gao, Zhaobing.(2013).The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel.TOXICOLOGY LETTERS,219(3),211-217. |
| MLA | Li, Ping,et al."The ethylene bis-dithiocarbamate fungicide Mancozeb activates voltage-gated KCNQ2 potassium channel".TOXICOLOGY LETTERS 219.3(2013):211-217. |
入库方式： OAI收割
来源：上海药物研究所
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