Recent advances in the mechanism of selenoamino acids toxicity in eukaryotic cells

• Published in: Biomolecular concepts Vol. 8; no. 2; pp. 93 - 104
• Main Authors: Lazard, Myriam, Dauplais, Marc, Blanquet, Sylvain, Plateau, Pierre
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 24.05.2017; Walter de Gruyter GmbH
• Subjects: Cytotoxicity; Eukaryotic Cells - drug effects; Genotoxicity; Homeostasis; Metabolic Networks and Pathways; Models, Biological; Molecular modelling; Organoselenium Compounds - toxicity; Oxidative stress; protein aggregation; Protein thiols; Reactive oxygen species; Saccharomyces cerevisiae - drug effects; Selenium; selenium toxicity; Selenoamino acids; Selenocysteine; Selenocysteine - toxicity; Selenomethionine; Selenomethionine - toxicity; Selenoproteins; Thiols; Toxicity; Trace elements; selenocysteine; selenomethionine; protein aggregation; reactive oxygen species; selenium toxicity
• ISSN: 1868-5021; 1868-5021; 1868-503X
• DOI: 10.1515/bmc-2017-0007

Selenium is an essential trace element due to its incorporation into selenoproteins with important biological functions. However, at high doses it is toxic. Selenium toxicity is generally attributed to the induction of oxidative stress. However, it has become apparent that the mode of action of seleno-compounds varies, depending on its chemical form and speciation. Recent studies in various eukaryotic systems, in particular the model organism , provide new insights on the cytotoxic mechanisms of selenomethionine and selenocysteine. This review first summarizes current knowledge on reactive oxygen species (ROS)-induced genotoxicity of inorganic selenium species. Then, we discuss recent advances on our understanding of the molecular mechanisms of selenocysteine and selenomethionine cytotoxicity. We present evidences indicating that both oxidative stress and ROS-independent mechanisms contribute to selenoamino acids cytotoxicity. These latter mechanisms include disruption of protein homeostasis by selenocysteine misincorporation in proteins and/or reaction of selenols with protein thiols.