Cargando…

Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits

Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K(+) (SK/K(Ca)) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurologi...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Jie, Yang, Li-Kun, Chen, Wei-Liang, Lin, Wei, Wang, Yu-Hai, Chen, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454010/
https://www.ncbi.nlm.nih.gov/pubmed/31001121
http://dx.doi.org/10.3389/fphar.2019.00325
_version_ 1783409484357435392
author Zhu, Jie
Yang, Li-Kun
Chen, Wei-Liang
Lin, Wei
Wang, Yu-Hai
Chen, Tao
author_facet Zhu, Jie
Yang, Li-Kun
Chen, Wei-Liang
Lin, Wei
Wang, Yu-Hai
Chen, Tao
author_sort Zhu, Jie
collection PubMed
description Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K(+) (SK/K(Ca)) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurological disorders. The aim of this study was to investigate the role of SK/K(Ca) channels in experimental SCI/R in rabbits. The expression of SK/K(Ca)1 protein significantly decreased in both cytoplasm and mitochondria in spinal cord tissues after SCI/R. Treatment with 2 mg/kg NS309, a pharmacological activator for SK/K(Ca) channel, attenuated SCI/R-induced neuronal loss, spinal cord edema and neurological dysfunction. These effects were still observed when the administration was delayed by 6 h after SCI/R initiation. NS309 decreased the levels of oxidative products and promoted activities of antioxidant enzymes in both serum and spinal cord tissues. The results of ELISA assay showed that NS309 markedly decreased levels of pro-inflammatory cytokines while increased anti-inflammatory cytokines levels after SCI/R. In addition, treatment with NS309 was shown to preserve mitochondrial respiratory complexes activities and enhance mitochondrial biogenesis. The results of western blot analysis showed that NS309 differentially regulated the expression of mitochondrial dynamic proteins. In summary, our results demonstrated that the SK/K(Ca) channel activator NS309 protects against SCI/R via anti-oxidative activity and inhibition of mitochondrial dysfunction, indicating a therapeutic potential of NS309 for SCI/R.
format Online
Article
Text
id pubmed-6454010
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-64540102019-04-18 Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits Zhu, Jie Yang, Li-Kun Chen, Wei-Liang Lin, Wei Wang, Yu-Hai Chen, Tao Front Pharmacol Pharmacology Spinal cord ischemia-reperfusion injury (SCI/R) is a rare but devastating disorder with a poor prognosis. Small conductance calcium-activated K(+) (SK/K(Ca)) channels are a family of voltage-independent potassium channels that are shown to participate in the pathological process of several neurological disorders. The aim of this study was to investigate the role of SK/K(Ca) channels in experimental SCI/R in rabbits. The expression of SK/K(Ca)1 protein significantly decreased in both cytoplasm and mitochondria in spinal cord tissues after SCI/R. Treatment with 2 mg/kg NS309, a pharmacological activator for SK/K(Ca) channel, attenuated SCI/R-induced neuronal loss, spinal cord edema and neurological dysfunction. These effects were still observed when the administration was delayed by 6 h after SCI/R initiation. NS309 decreased the levels of oxidative products and promoted activities of antioxidant enzymes in both serum and spinal cord tissues. The results of ELISA assay showed that NS309 markedly decreased levels of pro-inflammatory cytokines while increased anti-inflammatory cytokines levels after SCI/R. In addition, treatment with NS309 was shown to preserve mitochondrial respiratory complexes activities and enhance mitochondrial biogenesis. The results of western blot analysis showed that NS309 differentially regulated the expression of mitochondrial dynamic proteins. In summary, our results demonstrated that the SK/K(Ca) channel activator NS309 protects against SCI/R via anti-oxidative activity and inhibition of mitochondrial dysfunction, indicating a therapeutic potential of NS309 for SCI/R. Frontiers Media S.A. 2019-04-02 /pmc/articles/PMC6454010/ /pubmed/31001121 http://dx.doi.org/10.3389/fphar.2019.00325 Text en Copyright © 2019 Zhu, Yang, Chen, Lin, Wang and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhu, Jie
Yang, Li-Kun
Chen, Wei-Liang
Lin, Wei
Wang, Yu-Hai
Chen, Tao
Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title_full Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title_fullStr Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title_full_unstemmed Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title_short Activation of SK/K(Ca) Channel Attenuates Spinal Cord Ischemia-Reperfusion Injury via Anti-oxidative Activity and Inhibition of Mitochondrial Dysfunction in Rabbits
title_sort activation of sk/k(ca) channel attenuates spinal cord ischemia-reperfusion injury via anti-oxidative activity and inhibition of mitochondrial dysfunction in rabbits
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454010/
https://www.ncbi.nlm.nih.gov/pubmed/31001121
http://dx.doi.org/10.3389/fphar.2019.00325
work_keys_str_mv AT zhujie activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits
AT yanglikun activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits
AT chenweiliang activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits
AT linwei activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits
AT wangyuhai activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits
AT chentao activationofskkcachannelattenuatesspinalcordischemiareperfusioninjuryviaantioxidativeactivityandinhibitionofmitochondrialdysfunctioninrabbits