Mechanism of temporal gradients in shear-induced ERK1/2 activation and proliferation in endothelial cells
- 1 July 2001
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 281 (1) , H22-H29
- https://doi.org/10.1152/ajpheart.2001.281.1.h22
Abstract
The aim of the current study was to investigate the intracellular signaling cascade that leads to temporal gradients in shear (TGS)-induced endothelial cell proliferation, with a focus on the involvement of extracellular signal-regulated kinases 1 and 2 (ERK1/2). With the use of well-defined pulsatile, impulse, step, and ramp laminar flow profiles, we found that TGS (impulse flow and pulsatile flow) induced an enhanced and sustained (>30 min) phosphorylation of ERK1/2 relative to step flow (which contains a step increase in shear followed by steady shear), whereas steady shear (ramp flow) alone downregulated activated ERK1/2. Nitric oxide (NO) was found to mediate both the stimulatory effect of TGS and the inhibitory effect of steady shear on endothelial ERK1/2 phosphorylation. Reactive oxygen species (ROS) were also demonstrated to be associated with TGS-induced ERK1/2 phosphorylation. Both Gq/11 and Gi3 were necessary for the activation of ERK1/2 by TGS. Finally, the TGS-induced endothelial proliferative response was abolished by ERK1/2 inhibition. Our study demonstrated the essential role of G proteins, NO, and ROS in TGS-dependent ERK1/2 activation and proliferative response in vascular endothelial cells.Keywords
This publication has 44 references indexed in Scilit:
- The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acidPublished by Elsevier ,2003
- Mitogen-Activated Protein Kinase Pathway Mediates Peroxynitrite-Induced Apoptosis in Human Dopaminergic Neuroblastoma SH-SY5Y CellsBiochemical and Biophysical Research Communications, 1999
- JunB Forms the Majority of the AP-1 Complex and Is a Target for Redox Regulation by Receptor Tyrosine Kinase and G Protein-coupled Receptor Agonists in Smooth Muscle CellsPublished by Elsevier ,1999
- Nitric Oxide Regulates Cell Proliferation during Drosophila DevelopmentCell, 1996
- Steady Shear and Step Changes in Shear Stimulate Endothelium via Independent Mechanisms—Superposition of Transient and Sustained Nitric Oxide ProductionBiochemical and Biophysical Research Communications, 1996
- Human Gαq: cDNA and tissue distributionBiochimica et Biophysica Acta (BBA) - Biomembranes, 1996
- PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in VivoJournal of Biological Chemistry, 1995
- Fluid wall shear stress measurements in a model of the human abdominal aorta: oscillatory behavior and relationship to atherosclerosisAtherosclerosis, 1994
- Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c‐fos and junB in PC12 CellsJournal of Neurochemistry, 1994
- Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells.Journal of Clinical Investigation, 1984