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

Scientific Reports
Min Seok SongSo Yeong Lee

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.

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Citations

Feb 19, 2020·Molecular Membrane Biology·Jia LiuWei Zou
Jan 1, 2021·Frontiers in Cell and Developmental Biology·Magdalena BachmannErich Gulbins

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Methods Mentioned

BETA
transfection
ubiquitination
PCR
electrophoresis
protein assay
Assay

Software Mentioned

GraphPad Prism
GENEVESTIGATOR®
GENEVESTIGATOR
Metamorph
pClamp

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