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

• Published in: Metallomics 2020-11, Vol.12 (11), p.1693-171
• Main Authors: Nakano, Yukari, Shimoda, Mikako, Okudomi, Saki, Kawaraya, Sayuri, Kawahara, Masahiro, Tanaka, Ken-ichiro
• Format: Article
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/d0mt00136h

Excessive zinc ion (Zn 2+ ) release is induced in pathological situations and causes neuronal cell death. Previously, we have reported that copper ions (Cu 2+ ) markedly exacerbated Zn 2+ -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 Cu 2+ /Zn 2+ -induced neuronal cell death in GT1-7 cells. Seleno- l -methionine treatment clearly restored the Cu 2+ /Zn 2+ -induced decrease in the viable cell number and attenuated the Cu 2+ /Zn 2+ -induced cytotoxicity. Accordingly, the levels of ER stress-related factors (especially, CHOP and GADD34) and of phosphorylated JNK increased upon CuCl 2 and ZnCl 2 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 Cu 2+ /Zn 2+ -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 Cu 2+ /Zn 2+ -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. Seleno- l -methionine suppresses copper-enhanced zinc-induced neuronal cell death via induction of glutathione peroxidase.