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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.
J Clin Invest. 1993 Oct; 92(4):1866-74.JCI

Abstract

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.

Authors+Show Affiliations

Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7691889

Citation

Marui, N, et al. "Vascular Cell Adhesion Molecule-1 (VCAM-1) Gene Transcription and Expression Are Regulated Through an Antioxidant-sensitive Mechanism in Human Vascular Endothelial Cells." The Journal of Clinical Investigation, vol. 92, no. 4, 1993, pp. 1866-74.
Marui N, Offermann MK, Swerlick R, et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993;92(4):1866-74.
Marui, N., Offermann, M. K., Swerlick, R., Kunsch, C., Rosen, C. A., Ahmad, M., Alexander, R. W., & Medford, R. M. (1993). Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. The Journal of Clinical Investigation, 92(4), 1866-74.
Marui N, et al. Vascular Cell Adhesion Molecule-1 (VCAM-1) Gene Transcription and Expression Are Regulated Through an Antioxidant-sensitive Mechanism in Human Vascular Endothelial Cells. J Clin Invest. 1993;92(4):1866-74. PubMed PMID: 7691889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. AU - Marui,N, AU - Offermann,M K, AU - Swerlick,R, AU - Kunsch,C, AU - Rosen,C A, AU - Ahmad,M, AU - Alexander,R W, AU - Medford,R M, PY - 1993/10/1/pubmed PY - 1993/10/1/medline PY - 1993/10/1/entrez SP - 1866 EP - 74 JF - The Journal of clinical investigation JO - J Clin Invest VL - 92 IS - 4 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/7691889/Vascular_cell_adhesion_molecule_1__VCAM_1__gene_transcription_and_expression_are_regulated_through_an_antioxidant_sensitive_mechanism_in_human_vascular_endothelial_cells_ L2 - https://doi.org/10.1172/JCI116778 DB - PRIME DP - Unbound Medicine ER -