Abstract
Abstract Endothelial cells (ECs) are constantly exposed to blood pressure–induced mechanical strain. We have previously demonstrated that cyclic strain can induce gene expression of monocyte chemotactic protein-1 (MCP-1). The molecular mechanisms of gene induction by strain, however, remain unclear. Recent evidence indicates that intracellular reactive oxygen species (ROS) can act as a second messenger for signal transduction and thus affect gene expression. The potential role of ROS in strain-induced MCP-1 expression was investigated. ECs under cyclic strain induced a sustained elevated production of intracellular superoxide. ECs under strain or pretreated with either H 2 O 2 or xanthine oxidase/hypoxanthine induced MCP-1 expression. Strain- or oxidant-induced MCP-1 mRNA levels could be inhibited by treating ECs with catalase or antioxidant N -acetyl-cysteine (NAC). Functional analysis of MCP-1 promoter and site-specific mutations indicates that the proximal tissue plasminogen activator–responsive element (TRE) in the −60-bp promoter region is sufficient for strain or H 2 O 2 inducibility. Electrophoretic mobility shift assays demonstrated an increase of nuclear proteins binding to TRE sequences from ECs subsequent to strain or H 2 O 2 treatment. NAC or catalase pretreatment of ECs inhibited the strain- or H 2 O 2 -induced AP-1 binding. These results clearly indicate that cyclic strain inducibility of MCP-1 in ECs uses the interaction of AP-1 proteins with TRE sites via the elevation of intracellular ROS levels in strained ECs. These findings emphasize the importance of intracellular ROS in the modulation of hemodynamic force–induced gene expression in vascular ECs.
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Dates
Type | When |
---|---|
Created | 13 years, 2 months ago (June 11, 2012, 8:47 p.m.) |
Deposited | 1 year, 3 months ago (May 12, 2024, 4:53 p.m.) |
Indexed | 2 months ago (July 2, 2025, 2:34 p.m.) |
Issued | 28 years, 2 months ago (July 1, 1997) |
Published | 28 years, 2 months ago (July 1, 1997) |
Published Print | 28 years, 2 months ago (July 1, 1997) |
@article{Wung_1997, title={Cyclic Strain–Induced Monocyte Chemotactic Protein-1 Gene Expression in Endothelial Cells Involves Reactive Oxygen Species Activation of Activator Protein 1}, volume={81}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.81.1.1}, DOI={10.1161/01.res.81.1.1}, number={1}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Wung, B. S. and Cheng, J. J. and Hsieh, H. J. and Shyy, Y. J. and Wang, D. L.}, year={1997}, month=jul, pages={1–7} }