Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice

doi:10.1016/j.isci.2020.101617

	Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice
	Xu, Xiaoju 1; Xu, Xu 1; Hao, Yanping 2,3; Zhu, Xialin 1; Lu, Jian 1; Ouyang, Xingnan 1; Lu, Yin 1; Huang, Xi 1; Li, Yang 2,3; Wang, Jiaying 1
刊名	ISCIENCE
	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.
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
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000581985500072
内容类型	期刊论文
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.Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing 210023, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, 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.