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Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in vascular cells.
Roger F Duncan1, Hazel Peterson, Curt H Hagedorn
1Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, U.S.A. rduncan@hsc.usc.edu
The Biochemical Journal
|September 7, 2002
Summary
Increased activity of eukaryotic initiation factor 4E (eIF4E) drives cell growth and may contribute to early atherosclerosis by promoting the expression of growth-promoting proteins.
Area of Science:
- Molecular Biology
- Cell Biology
- Cardiovascular Research
Background:
- Dysregulated cell growth is a hallmark of atherosclerosis.
- Increased activity of eukaryotic initiation factor 4E (eIF4E) promotes cell growth.
- Oxidative stress from factors like oxidized low-density lipoprotein (oxLDL) is implicated in vascular disease.
Purpose of the Study:
- To investigate the role of eIF4E activation in the hyperproliferative response of vascular cells to oxidants.
- To determine if eIF4E phosphorylation is altered by oxLDL and other oxidants in vascular cells.
Main Methods:
- Treatment of endothelial cells, smooth muscle cells, and monocytes/macrophages with oxLDL, oxidized lipids, and model oxidants (H2O2, dimethyl naphthoquinone).
- Assessment of eIF4E phosphorylation and its association with active protein complexes.
- Evaluation of changes in other translation initiation factors (eIF4EBP, eIF2, eIF4B).
Main Results:
- Oxidant exposure induced a dose- and time-dependent increase in eIF4E phosphorylation in all tested vascular cells.
- Increased eIF4E phosphorylation correlated with a modest rise in overall translation rate.
- Antioxidants also promoted eIF4E phosphorylation, suggesting a complex regulatory role.
Conclusions:
- Increased eIF4E activity, indicated by phosphorylation, may play a role in early atherogenesis.
- This heightened activity could enhance the expression of mRNAs encoding growth-promoting proteins, contributing to vascular smooth muscle cell hyperproliferation.