PMID- 20042734
OWN - NLM
STAT- MEDLINE
DCOM- 20100524
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 298
IP  - 5
DP  - 2010 May
TI  - Thioredoxin 1 downregulates MCP-1 secretion and expression in human endothelial 
      cells by suppressing nuclear translocation of activator protein 1 and redox 
      factor-1.
PG  - C1170-9
LID - 10.1152/ajpcell.00223.2009 [doi]
AB  - To know whether thioredoxin 1 (Trx1) works for an antioxidant defense mechanism 
      in atherosclerosis, the effect of Trx1 on the release of monocyte chemoattractant 
      protein-1 (MCP-1), a potent chemoattractant for recruitment and accumulation of 
      monocytes/macrophages in the intima of artery vessel, was investigated in human 
      endothelial-like EA.hy 926 cells. It was found that overexpression of Trx1 
      suppressed, whereas knockdown of endogenous Trx1 enhanced, oxidized low-density 
      lipoprotein (oxLDL)-stimulated MCP-1 release and expression in the cells. It was 
      also observed that overexpression of Trx1 suppressed, whereas depletion of 
      endogenous Trx1 greatly promoted, nuclear translocation of c-Jun and the redox 
      factor-1 (Ref-1). Electrophoretic mobility shift assay showed significantly 
      reduced DNA-binding activity of activator protein-1 (AP-1) in Trx1-overexpressing 
      cells but apparently enhanced DNA binding activity of AP-1 in Trx1-knockdown 
      cells, indicating that nuclear Ref-1 rather than Trx1 itself finally dominates 
      the regulation of AP-1 activity, although Trx1 is considered to upregulate AP-1 
      activity. It was also observed that Trx1 depressed intracellular generation of 
      reactive oxygen species (ROS). Diphenyleneiodonium (DPI), the inhibitor of NADPH 
      oxidase, suppressed MCP-1 secretion, whereas transient expression of Nox1 
      enhanced transcription of MCP-1 in endothelial cells. Assays with AP-1 and MCP-1 
      luciferase reporters further demonstrated that transient expression of Trx1 
      significantly depressed the transcriptional activity of c-Jun/c-Fos and 
      consequent MCP-1 transcription. This study suggests that Trx1 inherently 
      suppresses MCP-1 expression in vascular endothelium and may prevent 
      atherosclerosis by depressing MCP-1 release. Besides the suppression of 
      intracellular ROS generation, the inhibition of nuclear translocation of AP-1 and 
      Ref-1 are mainly responsible for the downregulation of MCP-1 by Trx1.
FAU - Chen, Beidong
AU  - Chen B
AD  - Institute of Biophysics, Chinese Academy of Sciences, Beijing Normal University, 
      Beijing, China.
FAU - Guan, Dandan
AU  - Guan D
FAU - Cui, Zong Jie
AU  - Cui ZJ
FAU - Wang, Xian
AU  - Wang X
FAU - Shen, Xun
AU  - Shen X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091230
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor AP-1)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 4.2.99.18 (APEX1 protein, human)
RN  - EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Chemokine CCL2/genetics/*metabolism
MH  - DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Gene Deletion
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Reactive Oxygen Species
MH  - Thioredoxins/*metabolism
MH  - Transcription Factor AP-1/genetics/*metabolism
EDAT- 2010/01/01 06:00
MHDA- 2010/05/25 06:00
CRDT- 2010/01/01 06:00
PHST- 2010/01/01 06:00 [entrez]
PHST- 2010/01/01 06:00 [pubmed]
PHST- 2010/05/25 06:00 [medline]
AID - ajpcell.00223.2009 [pii]
AID - 10.1152/ajpcell.00223.2009 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2010 May;298(5):C1170-9. doi: 
      10.1152/ajpcell.00223.2009. Epub 2009 Dec 30.