Inorganic arsenic modulates the expression of selenoproteins in mouse embryonic stem cell.
At least 25 selenoproteins in humans and 24 homologues in rodents have been identified. They play important roles in antioxidation, redox regulation and detoxification. The modulation of the expression of selenoproteins by inorganic arsenic (iAs) exposure may highlight the molecular mechanism for the arsenic toxicity. To investigate the effects of iAs exposure on the expression of selenoproteins, we determined how addition of iAs to culture medium affected all known selenoproteins in the mouse embryonic stem (ES) cells. Separated groups of ES cells were treated with arsenite (iAsIII) (0.25-0.5microM), arsenate (iAsV) (1.0-2.0microM) and co-treatment with sodium selenite (SeIV) (0.5microM). The mRNA levels of all selenoproteins were detected by real time quantitative PCR. The up-regulated selenoproteins were confirmed by immunoblotting analysis and enzymatic activity detection. Results showed that CGR8 cells treated with iAsIII (0.25-0.5microM) and iAsV (2.0microM) displayed significant increases of cellular reactive oxygen species (ROS) generation and nuclear accumulation of the transcription factor NF-E2-related factor 2 (Nrf2). Treatments of iAsIII (0.5microM) or iAsV (2.0microM) for 24h caused significant increases in the expression of the antioxidant selenoproteins (Gpx1, Gpx4, and Tr1), whereas led to significant decreases in the mRNA levels of selenoprotein H and some endoplasmic reticulum (ER) located selenoproteins (15-Sep, SelK, SelM, and SelS). Additionally, supplement of SeIV (0.5microM) could restore most of the down-regulated selenoproteins. These results suggested that iAs exposure modulated not only the antioxidant selenoproteins but also the ER stress associated selenoproteins. Further studies are required to clarify whether these modulated selenoproteins genes are targets for selenium supplement in the defense against the toxicity of iAs.
Department of Chemistry, Key Laboratory for Atomic and Molecular Nanosciences of Education Ministry, Tsinghua University, 100084 Beijing, PR China.
Zhi
Z
Huang
Jun
J
Li
Sichun
S
Zhang
Xinrong
X
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001149:Arsenates / Q000633:toxicity*; D018053:Arsenites / Q000633:toxicity*; D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051140:Selenoproteins / Q000096:biosynthesis* / Q000235:genetics; D018038:Sodium Selenite / Q000494:pharmacology
D001149:Arsenates; D018053:Arsenites; D051267:NF-E2-Related Factor 2; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051140:Selenoproteins; D018038:Sodium Selenite