Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice
文献类型：期刊论文
| 作者 | Xu, Xiaoju2; Xu, Xu2; Hao, Yanping1,3; Zhu, Xialin2; Lu, Jian2; Ouyang, Xingnan2; Lu, Yin2; Huang, Xi2; Li, Yang1,3 ; Wang, Jiaying2
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| 刊名 | ISCIENCE
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| 出版日期 | 2020-10-23 |
| 卷号 | 23期号:10页码:56 |
| DOI | 10.1016/j.isci.2020.101617 |
| 通讯作者 | Li, Yang(liyang@simm.ac.cn) ; Wang, Jiaying(wangjy@njucm.edu.cn) ; Shen, Xu(xshen@njucm.edu.cn) |
| 英文摘要 | Diabetic peripheral neuropathy (DPN) is a common diabetic complication and has yet no efficient medication. Here, we report that antispasmodic drug drofenine (Dfe) blocks Kv2.1 and ameliorates DPN-like pathology in diabetic mice. The underlying mechanisms are investigated against the DPN mice with in vivo Kv2.1 knockdown through adeno associated virus AAV9-Kv2.1-RNAi. Streptozotocin (STZ) induced type 1 or db/db type 2 diabetic mice with DPN exhibited a high level of Kv2.1 protein in dorsal root ganglion (DRG) tissue and a suppressed neurite outgrowth in DRG neuron. Dfe promoted neurite outgrowth by inhibiting Kv2.1 channel and/or Kv2.1 mRNA and protein expression level. Moreover, it suppressed inflammation by repressing I kappa B alpha/NF-kappa B signaling, inhibited apoptosis by regulating Kv2.1-mediated Bcl-2 family proteins and Caspase-3 and ameliorated mitochondrial dysfunction through Kv2.1/CaMKK beta/AMPK/PGC1 alpha pathway. Our work supports that Kv2.1 inhibition is a promisingly therapeutic strategy for DPN and highlights the potential of Dfe in treating this disease. |
| WOS关键词 | NF-KAPPA-B ; GATED POTASSIUM CHANNELS ; ACID COMBINATION THERAPY ; PRIMARY SENSORY NEURONS ; ROOT GANGLIA NEURONS ; LIPOIC ACID ; MITOCHONDRIAL BIOENERGETICS ; OXIDATIVE STRESS ; APOPTOSIS ; GLUCOSE |
| 资助项目 | National Science & Technology Major Project ''Key New Drug Creation and Manufacturing Program'' China[2018ZX09711002] ; National Natural Science Foundation of China for Young Scientists of China[81703806] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province[KYCX18_1600] ; Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese MateriaMedica[JKLPSE201801] ; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions of Jiangsu Higher Education Institutions (PAPD) ; Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine) ; Innovative Research Team of Six Talent Peaks Project in Jiangsu Province[TD-SWYY-013] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000581985500072 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296181]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Yang; Wang, Jiaying; Shen, Xu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing 210023, Jiangsu, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Xiaoju,Xu, Xu,Hao, Yanping,et al. Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice[J]. ISCIENCE,2020,23(10):56. |
| APA | Xu, Xiaoju.,Xu, Xu.,Hao, Yanping.,Zhu, Xialin.,Lu, Jian.,...&Shen, Xu.(2020).Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice.ISCIENCE,23(10),56. |
| MLA | Xu, Xiaoju,et al."Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice".ISCIENCE 23.10(2020):56. |
入库方式： OAI收割
来源：上海药物研究所
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