PMID- 7691889
OWN - NLM
STAT- MEDLINE
DCOM- 19931112
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 92
IP  - 4
DP  - 1993 Oct
TI  - Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are 
      regulated through an antioxidant-sensitive mechanism in human vascular 
      endothelial cells.
PG  - 1866-74
AB  - 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.
FAU - Marui, N
AU  - Marui N
AD  - Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 
      30322.
FAU - Offermann, M K
AU  - Offermann MK
FAU - Swerlick, R
AU  - Swerlick R
FAU - Kunsch, C
AU  - Kunsch C
FAU - Rosen, C A
AU  - Rosen CA
FAU - Ahmad, M
AU  - Ahmad M
FAU - Alexander, R W
AU  - Alexander RW
FAU - Medford, R M
AU  - Medford RM
LA  - eng
GR  - P01 HL48667/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antioxidants)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DNA Probes)
RN  - 0 (E-Selectin)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Base Sequence
MH  - Binding Sites
MH  - Blotting, Northern
MH  - Cell Adhesion Molecules/analysis/*biosynthesis/*genetics
MH  - Cell Nucleus/metabolism
MH  - Cells, Cultured
MH  - DNA Probes
MH  - E-Selectin
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression/drug effects
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/biosynthesis
MH  - Humans
MH  - Intercellular Adhesion Molecule-1
MH  - Interleukin-1/*pharmacology
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - Oligodeoxyribonucleotides/chemical synthesis/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/drug effects/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Umbilical Veins
MH  - Vascular Cell Adhesion Molecule-1
PMC - PMC288351
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
PMCR- 1993/10/01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
PHST- 1993/10/01 00:00 [pmc-release]
AID - 10.1172/JCI116778 [doi]
PST - ppublish
SO  - J Clin Invest. 1993 Oct;92(4):1866-74. doi: 10.1172/JCI116778.