Stimulation of transcription factors NF kappa B and AP1 in endothelial cells subjected to shear stress.
Hemodynamic shear stress forces influence several important endothelial genes associated with arterial relaxation, pro/anti-coagulation, and growth control; however, the regulatory pathways remain unclear. Here we demonstrate stimulation of DNA binding activities of nuclear factor kappa B (NF kappa B), a member of the Rel Family of transcription factors, and nuclear factor activator protein-1 (AP-1) following exposure of endothelial cells to unidirectional shear stress in laminar flow. NF kappa B binding was stimulated within 30 minutes, reaching and maintaining maximal levels at 1 hour. DNA binding activity was inhibited by pre-incubation of nuclear extract with antibody directed against NF kappa B p65 subunit. AP-1 binding activity was biphasic, rising fourfold within 20 minutes and returning to basal levels before steadily increasing by 2 hours to a high level relative to basal values. These protein kinase C-coupled transcriptional factors may modulate endothelial genes that are shear stress-responsive and that possess appropriate binding sites in the promoter region.
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Department of Pathology, Pritzker School of Medicine, University of Chicago, IL 60637.
Mercurius
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Davies
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D000818:Animals; D001011:Aorta; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002478:Cells, Cultured; D016384:Consensus Sequence; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000302:isolation & purification / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000302:isolation & purification / Q000378:metabolism*; D013314:Stress, Mechanical; D013997:Time Factors
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA