Cadmium (Cd) as a ubiquitous toxic heavy metal in the environment, causes severe hazards to human health, such as cellular stress and organ injury. Selenium (Se) was reported to reduce Cd toxicity and the mechanisms have been intensively studied so far. However, it is not yet crystal clear whether the protective effect of Se against Cd-induced cytotoxicity is related to selenoproteins in nerve cells or not. In this study, we found that Cd inhibited selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1) and decreased the expression level of TrxR1, resulting in cellular oxidative stress, and Se supplements ameliorated Cd-induced cytotoxicity in SH-SY5Y cells. Mechanistically, the detoxification of Se against Cd is attributed to the increase of the cellular TrxR activity and upregulated TrxR1 protein level, culminating in strengthened antioxidant capacity. Results showed that Se supplements attenuated the ROS production and apoptosis in SH-SY5Y cells, and significantly mitigated Cd-induced SH-SY5Y cell death. This study may be a valuable reference for shedding light on the mechanism of Cd-induced cytotoxicity and the role of TrxR1 in Se-mitigated cytotoxicity of Cd in neuroblast cells, which may be helpful for understanding the therapeutic potential of Cd and Se in treating or preventing neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD).
Keywords: Apoptosis; Cadmium; Cytotoxicity; Reactive oxygen species; Selenium; Thioredoxin reductase 1.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.