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 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 S

SUBMITTER: Song MS 

PROVIDER: S-EPMC5437029 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature