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Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells

MARUI, N ; OFFERMANN, M. K ; SWERLICK, R ; KUNSCH, C ; ROSEN, C. A ; MUSHTAQ AHMAD ; ALEXANDER, R. W ; MEDFORD, R. M

The Journal of clinical investigation, 1993-10, Vol.92 (4), p.1866-1874 [Periódico revisado por pares]

Ann Arbor, MI: American Society for Clinical Investigation

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Título:
Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells
Autor: MARUI, N ; OFFERMANN, M. K ; SWERLICK, R ; KUNSCH, C ; ROSEN, C. A ; MUSHTAQ AHMAD ; ALEXANDER, R. W ; MEDFORD, R. M
Assuntos: Antioxidants - pharmacology ; Atherosclerosis (general aspects, experimental research) ; Base Sequence ; Binding Sites ; Biological and medical sciences ; Blood and lymphatic vessels ; Blotting, Northern ; Cardiology. Vascular system ; Cell Adhesion Molecules - analysis ; Cell Adhesion Molecules - biosynthesis ; Cell Adhesion Molecules - genetics ; Cell Nucleus - metabolism ; Cells, Cultured ; DNA Probes ; E-Selectin ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Enzyme-Linked Immunosorbent Assay ; Gene Expression - drug effects ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - physiology ; Glyceraldehyde-3-Phosphate Dehydrogenases - biosynthesis ; Humans ; Intercellular Adhesion Molecule-1 ; Interleukin-1 - pharmacology ; Medical sciences ; Molecular Sequence Data ; NF-kappa B - metabolism ; Oligodeoxyribonucleotides - chemical synthesis ; Oligodeoxyribonucleotides - metabolism ; Promoter Regions, Genetic ; Recombinant Proteins - pharmacology ; RNA, Messenger - drug effects ; RNA, Messenger - metabolism ; Transcription, Genetic - drug effects ; Tumor Necrosis Factor-alpha - pharmacology ; Umbilical Veins ; Vascular Cell Adhesion Molecule-1
É parte de: The Journal of clinical investigation, 1993-10, Vol.92 (4), p.1866-1874
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: Ann Arbor, MI: American Society for Clinical Investigation
Idioma: Inglês

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Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells

MARUI, N ; OFFERMANN, M. K ; SWERLICK, R ; KUNSCH, C ; ROSEN, C. A ; MUSHTAQ AHMAD ; ALEXANDER, R. W ; MEDFORD, R. M

Ann Arbor, MI: American Society for Clinical Investigation

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