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

• Published in: Metallomics 2020-11, Vol.12 (11), p.1693-1701
• Main Authors: Nakano, Yukari, Shimoda, Mikako, Okudomi, Saki, Kawaraya, Sayuri, Kawahara, Masahiro, Tanaka, Ken-Ichiro
• Format: Article
• Language: English
• Subjects: Amino acids; Apoptosis; Cell death; Cell number; Cellular stress response; Copper; Copper chloride; Cytotoxicity; Endoplasmic reticulum; GADD34 protein; Glutathione; Glutathione peroxidase; Kinases; Methionine; Mortality; Neurological diseases; Oxidative stress; Peroxidase; Pretreatment; Reactive oxygen species; Selenium; Signal transduction; Toxicity; Trace elements; Transcription factors; Zinc; Zinc chloride
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/d0mt00136h

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