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Neuroprotective Effect of Sea Anemone Polypeptide BDS‐II Toxin: Relationship between Neurodegenerative Disease and Kv3.4
Author(s) -
Song Min Seok,
Ryu Pan Dong,
Lee So Yeong
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.845.15
Subject(s) - potassium channel , neuroprotection , oxidative stress , membrane potential , chemistry , cytochrome c , pharmacology , mitochondrion , reactive oxygen species , channel blocker , microbiology and biotechnology , hypoxia (environmental) , sh sy5y , biophysics , biochemistry , biology , cell culture , oxygen , calcium , genetics , organic chemistry , neuroblastoma
Voltage‐gated potassium channels of the Shaw‐related subfamily (Kv3.1–Kv3.4), display rapid activation and deactivation kinetics as well as relatively large conductance. Kv3.4 is an oxidation sensitive channel, where channel conductance is regulated by oxidation of cysteine residues of the channel by reactive oxygen species. However, the function of this Kv3.4 oxidation sensitivity is not well known. This study demonstrates a relationship between Kv3.4 and Parkinson's disease, a typical neurodegenerative disease, which is generally characterized by excessive oxidative stress. Both hypoxia and 1‐methyl‐4‐phenylpyridinium (MPP + ) treatment are known to induce oxidative stress. Interestingly, the expression level and potassium currents of Kv3.4 were decreased by CoCl 2 ‐induced hypoxia in SH‐SY5Y cells (an in vitro Parkinson's disease model). We used a blood‐depressing substance (BDS), a Kv3.4 specific blocker, before MPP + treatment to mimic the decreased Kv3.4 potassium currents occurring in CoCl 2 ‐induced hypoxia. BDS treatment protected SH‐SY5Y cells against MPP + ‐induced cell death. BDS treatment also blocked cytochrome c release from the mitochondria to the cytosol and suppressed caspase‐3 activation induced by MPP + treatment; consequently, the original mitochondrial membrane potential was maintained. In the absence of BDS, MPP + treatment depolarized the mitochondrial membrane potential. We also found that hypoxia inducible factor (HIF) is involved in these phenomena. Down‐regulation of Kv3.4 expression by CoCl 2 ‐induced hypoxia was recovered by blocking HIF‐1a. Taken together, these data support a neuroprotective effect of BDS in SH‐SY5Y cells. The Kv3.4 channel is involved in cell death and HIF may play a role in the underlying mechanism.