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Seleno-l-methionine suppresses copper-enhanced zinc-induced neuronal cell death via induction of glutathione peroxidase

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Abstract

Excessive zinc ion (Zn2+) release is induced in pathological situations and causes neuronal cell death. Previously, we have reported that copper ions (Cu2+) markedly exacerbated Zn2+-induced neuronal cell death by potentiating oxidative stress, the endoplasmic reticulum (ER) stress response, and the activation of the c-Jun amino-terminal kinase (JNK) signaling pathway. In contrast, selenium (Se), an essential trace element, and amino acids containing selenium (such as seleno-L-methionine) have been reported to inhibit stress-induced neuronal cell death and oxidative stress. Thus, we investigated the effect of seleno-L-methionine on Cu2+/Zn2+-induced neuronal cell death in GT1–7 cells. Seleno-L-methionine treatment clearly restored the Cu2+/Zn2+-induced decrease in the viable cell number and attenuated the Cu2+/Zn2+-induced cytotoxicity. Accordingly, the levels of ER stress-related factors (especially, CHOP and GADD34) and of phosphorylated JNK increased upon CuCl2 and ZnCl2 co-treatment, whereas pre-treatment with seleno-L-methionine significantly suppressed these upregulations. Analysis of reactive oxygen species (ROS) as upstream factors of these pathways revealed that Cu2+/Zn2+-induced ROS production was clearly suppressed by seleno-L-methionine treatment. Finally, we found that seleno-L-methionine induced the antioxidative protein, glutathione peroxidase. Taken together, our findings suggest that seleno-L-methionine suppresses Cu2+/Zn2+-induced neuronal cell death and oxidative stress via induction of glutathione peroxidase. Thus, we think that seleno-L-methionine may help prevent refractory neurological diseases.

Graphical abstract: Seleno-l-methionine suppresses copper-enhanced zinc-induced neuronal cell death via induction of glutathione peroxidase

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Supplementary files

Article information


Submitted
07 Jun 2020
Accepted
04 Sep 2020
First published
04 Sep 2020

Metallomics, 2020, Advance Article
Article type
Paper

Seleno-L-methionine suppresses copper-enhanced zinc-induced neuronal cell death via induction of glutathione peroxidase

Y. Nakano, M. Shimoda, S. Okudomi, S. Kawaraya, M. Kawahara and K. Tanaka, Metallomics, 2020, Advance Article , DOI: 10.1039/D0MT00136H

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