Cyclic strain-induced monocyte chemotactic protein-1 (MCP-1) gene expression in endothelial cells involves reactive oxygen species activation of AP-1
Journal
FASEB Journal
Journal Volume
11
Journal Issue
3
Date Issued
1997
Author(s)
Abstract
We have previously shown that cyclic strain can induce gene expression of MCP-1 in endothelial cells (ECs). The molecular mechanisms of gene induction by strain remain unclear. Recent studies indicate that intracellular reactive oxygen species (ROS) can act as second messengers. The potential role of ROS in strain-induced MCP-1 expression was examined. ECs under strain (11%) induced a sustained elevated production of intracellular superoxide. ECs under strain or treated with H2O2 or xanthine oxidase/hypoxanthine induced MCP-1 expression. Strain- or oxidant- induced MCP-1 mRNA levels could be inhibited by treating ECs with antioxidant (catalase or N-aceyl-cysteine (NAC)). Functional analysis of MCP-1 promoter and site-specific mutations indicate that the proximal TRE site in the -60 bp promoter region is sufficient for strain or H2O2 inducibility. Electrophoretic mobility shift assays demonstrated an increase of nuclear proteins binding to TRE sequences from ECs subsequent to strain or H2O2 treatment. NAC pretreatment of ECs inhibited the strain- or H2O2- induced AP-1 binding. These results indicate that cyclic strain inducibility of MCP-1 in ECs utilizes the interaction of AP-1 proteins with TRE site via the elevation of intracellular ROS levels in strained ECs. Our findings thus emphasize the importance of ROS in the modulation of hemodynamic forces-induced gene expression in vascular ECs.
Type
journal article