Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells
| Autor: | Nobuyuki Marui, Mushtaq Ahmad, C. Kunsch, Robert Alexander, C. A. Rosen, Russell M. Medford, M. K. Offermann, Robert A. Swerlick |
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| Rok vydání: | 1993 |
| Předmět: |
Umbilical Veins
Transcription Genetic medicine.medical_treatment Molecular Sequence Data Gene Expression Vascular Cell Adhesion Molecule-1 Enzyme-Linked Immunosorbent Assay Antioxidants chemistry.chemical_compound Pyrrolidine dithiocarbamate Gene expression E-selectin medicine Humans RNA Messenger VCAM-1 Promoter Regions Genetic Cell adhesion Cells Cultured Cell Nucleus Regulation of gene expression Binding Sites Base Sequence biology Tumor Necrosis Factor-alpha Cell adhesion molecule NF-kappa B Glyceraldehyde-3-Phosphate Dehydrogenases General Medicine Blotting Northern Intercellular Adhesion Molecule-1 Molecular biology Recombinant Proteins Cytokine Gene Expression Regulation Oligodeoxyribonucleotides chemistry biology.protein Endothelium Vascular DNA Probes E-Selectin Cell Adhesion Molecules Research Article Interleukin-1 |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0021-9738 |
| Popis: | Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. Regulation of VCAM-1 gene expression may be coupled to oxidative stress through specific reduction-oxidation (redox) sensitive transcriptional or posttranscriptional regulatory factors. In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC). Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC). PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion. In a distinct pattern, PDTC partially inhibited E-selectin gene expression in response to TNF alpha but not to LPS, IL-1 beta, or PIC. TNF alpha and LPS-mediated transcriptional activation of the human VCAM-1 promoter through NF-kappa B-like DNA enhancer elements and associated NF-kappa B-like DNA binding proteins was inhibited by PDTC. These studies suggest a molecular linkage between an antioxidant sensitive transcriptional regulatory mechanism and VCAM-1 gene expression that expands on the notion of oxidative stress as an important regulatory signal in the pathogenesis of atherosclerosis. |
| Databáze: | OpenAIRE |
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