Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells.
To know if thioredoxin reductase 1 (TrxR1) plays a role in antioxidant defense mechanisms against atherosclerosis, effect of TrxR1 on expression/release of monocyte chemoattractant protein (MCP-1) was investigated in activated human endothelial-like EAhy926 cells. The MCP-1 release and expression, cellular generation of reactive oxygen species (ROS), nuclear translocation and DNA-binding activity of NF-kappaB subunit p65 were assayed in cells either overexpressing recombinant TrxR1 or having their endogenous TrxR1 knocked down. It was found that overexpression of TrxR1 enhanced, while knockdown of TrxR1 reduced MCP-1 release and expression. Upregulation of MCP-1 by TrxR1 was associated with increasing generation of intracellular ROS generation, enhanced nuclear translocation and DNA-binding activity of NF-kappaB. Assay using NF-kappaB reporter revealed that TrxR1 upregulated transcriptional activity of NF-kappaB. This study suggests that TrxR1 enhances ROS generation, NF-kappaB activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque.
Liu
Zhen-Bo
ZB
Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing, China.
Shen
Xun
X
D021581:Active Transport, Cell Nucleus; D050197:Atherosclerosis / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1