Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death

Abstract The Kv3.4 channel is characterized by fast inactivation and sensitivity to oxidation. However, the physiological role of Kv3.4 as an oxidation-sensitive channel has yet to be investigated. Here, we demonstrate that Kv3.4 plays a pivotal role in oxidative stress-related neural cell damage as...

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Autores principales:	Min Seok Song, Pan Dong Ryu, So Yeong Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/43d782e9288f4a689d0640081824cb8f
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spelling	oai:doaj.org-article:43d782e9288f4a689d0640081824cb8f2021-12-02T16:08:21ZKv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death10.1038/s41598-017-02129-w2045-2322https://doaj.org/article/43d782e9288f4a689d0640081824cb8f2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02129-whttps://doaj.org/toc/2045-2322Abstract The Kv3.4 channel is characterized by fast inactivation and sensitivity to oxidation. However, the physiological role of Kv3.4 as an oxidation-sensitive channel has yet to be investigated. Here, we demonstrate that Kv3.4 plays a pivotal role in oxidative stress-related neural cell damage as an oxidation-sensitive channel and that HIF-1α down-regulates Kv3.4 function, providing neuroprotection. MPP+ and CoCl2 are reactive oxygen species (ROS)-generating reagents that induce oxidative stress. However, only CoCl2 decreases the expression and function of Kv3.4. HIF-1α, which accumulates in response to CoCl2 treatment, is a key factor in Kv3.4 regulation. In particular, mitochondrial Kv3.4 was more sensitive to CoCl2. Blocking Kv3.4 function using BDS-II, a Kv3.4-specific inhibitor, protected SH-SY5Y cells against MPP+-induced neural cell death. Kv3.4 inhibition blocked MPP+-induced cytochrome c release from the mitochondrial intermembrane space to the cytosol and mitochondrial membrane potential depolarization, which are characteristic features of apoptosis. Our results highlight Kv3.4 as a possible new therapeutic paradigm for oxidative stress-related diseases, including Parkinson’s disease.Min Seok SongPan Dong RyuSo Yeong LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min Seok Song Pan Dong Ryu So Yeong Lee Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
description	Abstract The Kv3.4 channel is characterized by fast inactivation and sensitivity to oxidation. However, the physiological role of Kv3.4 as an oxidation-sensitive channel has yet to be investigated. Here, we demonstrate that Kv3.4 plays a pivotal role in oxidative stress-related neural cell damage as an oxidation-sensitive channel and that HIF-1α down-regulates Kv3.4 function, providing neuroprotection. MPP+ and CoCl2 are reactive oxygen species (ROS)-generating reagents that induce oxidative stress. However, only CoCl2 decreases the expression and function of Kv3.4. HIF-1α, which accumulates in response to CoCl2 treatment, is a key factor in Kv3.4 regulation. In particular, mitochondrial Kv3.4 was more sensitive to CoCl2. Blocking Kv3.4 function using BDS-II, a Kv3.4-specific inhibitor, protected SH-SY5Y cells against MPP+-induced neural cell death. Kv3.4 inhibition blocked MPP+-induced cytochrome c release from the mitochondrial intermembrane space to the cytosol and mitochondrial membrane potential depolarization, which are characteristic features of apoptosis. Our results highlight Kv3.4 as a possible new therapeutic paradigm for oxidative stress-related diseases, including Parkinson’s disease.
format	article
author	Min Seok Song Pan Dong Ryu So Yeong Lee
author_facet	Min Seok Song Pan Dong Ryu So Yeong Lee
author_sort	Min Seok Song
title	Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
title_short	Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
title_full	Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
title_fullStr	Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
title_full_unstemmed	Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death
title_sort	kv3.4 is modulated by hif-1α to protect sh-sy5y cells against oxidative stress-induced neural cell death
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/43d782e9288f4a689d0640081824cb8f
work_keys_str_mv	AT minseoksong kv34ismodulatedbyhif1atoprotectshsy5ycellsagainstoxidativestressinducedneuralcelldeath AT pandongryu kv34ismodulatedbyhif1atoprotectshsy5ycellsagainstoxidativestressinducedneuralcelldeath AT soyeonglee kv34ismodulatedbyhif1atoprotectshsy5ycellsagainstoxidativestressinducedneuralcelldeath
_version_	1718384524618891264

Kv3.4 is modulated by HIF-1α to protect SH-SY5Y cells against oxidative stress-induced neural cell death

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