Tags

Type your tag names separated by a space and hit enter

NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production.
J Mol Cell Cardiol. 2000 Aug; 32(8):1499-508.JM

Abstract

Oxidation-reduction (redox) coupled mechanisms play an important role in the regulation of cell surface adhesion molecule expression. In endothelial cells membrane-bound NADH/NADPH oxidase is a significant source of intracellular superoxide (O(2)(-)) production. We explored the role of flavin containing proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene expression in human aortic endothelial cells (HAECs) and human dermal microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(-)production within 5 min as determined by lucigenin chemiluminescence analysis of whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation. However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF- alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter gene constructs in transiently transfected HMECs. These data suggest that flavin binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not necessary for NF- kappa B activation or for transactivation of NF- kappa B driven promoters.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

10900176

Citation

Tummala, P E., et al. "NF- Kappa B Independent Suppression of Endothelial Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Gene Expression By Inhibition of Flavin Binding Proteins and Superoxide Production." Journal of Molecular and Cellular Cardiology, vol. 32, no. 8, 2000, pp. 1499-508.
Tummala PE, Chen XL, Medford RM. NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production. J Mol Cell Cardiol. 2000;32(8):1499-508.
Tummala, P. E., Chen, X. L., & Medford, R. M. (2000). NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production. Journal of Molecular and Cellular Cardiology, 32(8), 1499-508.
Tummala PE, Chen XL, Medford RM. NF- Kappa B Independent Suppression of Endothelial Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 Gene Expression By Inhibition of Flavin Binding Proteins and Superoxide Production. J Mol Cell Cardiol. 2000;32(8):1499-508. PubMed PMID: 10900176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production. AU - Tummala,P E, AU - Chen,X L, AU - Medford,R M, PY - 2000/7/20/pubmed PY - 2000/10/14/medline PY - 2000/7/20/entrez SP - 1499 EP - 508 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 32 IS - 8 N2 - Oxidation-reduction (redox) coupled mechanisms play an important role in the regulation of cell surface adhesion molecule expression. In endothelial cells membrane-bound NADH/NADPH oxidase is a significant source of intracellular superoxide (O(2)(-)) production. We explored the role of flavin containing proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene expression in human aortic endothelial cells (HAECs) and human dermal microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(-)production within 5 min as determined by lucigenin chemiluminescence analysis of whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation. However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF- alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter gene constructs in transiently transfected HMECs. These data suggest that flavin binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not necessary for NF- kappa B activation or for transactivation of NF- kappa B driven promoters. SN - 0022-2828 UR - https://www.unboundmedicine.com/medline/citation/10900176/NF__kappa_B_independent_suppression_of_endothelial_vascular_cell_adhesion_molecule_1_and_intercellular_adhesion_molecule_1_gene_expression_by_inhibition_of_flavin_binding_proteins_and_superoxide_production_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(00)91183-0 DB - PRIME DP - Unbound Medicine ER -