Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice
© 2020 The Author(s)..
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 IκBα/NF-κB signaling, inhibited apoptosis by regulating Kv2.1-mediated Bcl-2 family proteins and Caspase-3 and ameliorated mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC1α 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
iScience - 23(2020), 10 vom: 23. Okt., Seite 101617 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Xiaoju [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 23.10.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2020.101617 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316580759 |
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| 520 | |a © 2020 The Author(s). | ||
| 520 | |a 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 IκBα/NF-κB signaling, inhibited apoptosis by regulating Kv2.1-mediated Bcl-2 family proteins and Caspase-3 and ameliorated mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC1α 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Immunology | |
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| 700 | 1 | |a Hao, Yanping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xialin |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Xingnan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiaying |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xu |e verfasserin |4 aut | |
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