Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Selenium is an essential trace element and is incorporated into the active center of reductases and other enzymes as selenocysteine to perform important physiological functions. Selenoprotein P (SeP) is a unique secreted plasma protein containing 10 selenocysteine residues in one molecule and plays an important role in selenium transport. Unlike cysteine, selenocysteine has a selenol side chain, which is highly nucleophilic and is expected to be susceptible to adduct formation by various electrophiles. However, how the adduct formation of electrophiles on SeP affects its selenium transport and supply activity, as well as its intracellular selenium metabolism, is not well understood. In this study, we developed a new method to analyze adduct formation to selenocysteine residues and attempted to elucidate the effects of adduct formation to SeP by various electrophiles and oxidants on selenium supply and metabolism.
We found that electrophiles in food and the environment inhibit the selenium-supplying activity of SeP and alter selenium metabolism, and that the lysosomal degradation of SeP is not inhibited, but the subsequent selenium catabolism is inhibited, resulting in decreased glutathione peroxidase expression. These results indicate for the first time that adduct formation of SeP in blood induces abnormal selenium metabolism and can disturb the oxidative stress defense mechanism. On the other hand, we have also found that excessive SeP production is associated with various diseases, and we are investigating the possibility that controlling adduct formation to SeP could be applied to the prevention and treatment of diseases caused by reduction stress.
