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Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells.

Authors
Jeong, EM; Moon, CH; Kim, CS; Lee, SH; Baik, EJ; Moon, CK; Jung, YS
Citation
Biochemical and biophysical research communications, 320(3):887-892, 2004
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
Cadmium (Cd), a ubiquitous heavy metal, has been shown to accumulate in the central nervous system, especially outside of the blood-brain barrier (BBB), suggesting a potential toxicity to nervous tissue. Thus, we investigated the effect of Cd on intercellular adhesion molecule-1 (ICAM-1) expression, as an indicator of BBB injury, in mouse brain microvessel endothelial cells (bEnd.3 cells). The treatment with Cd increased the expression of ICAM-1 at the levels of protein and mRNA, and these increases were almost completely inhibited by a specific NF-kappaB inhibitor SN50. The treatment with Cd induced the translocation of NF-kappaB from cytosolic to membrane fraction and increased DNA binding activity of NF-kappaB, and this NF-kappaB activation was inhibited by SN50. Interestingly, Cd did not trigger the degradation of IkappaBalpha, suggesting that Cd-induced ICAM-1 expression is mediated through IkappaBalpha degradation-independent pathway. Instead, tyrosine phosphorylation of IkappaBalpha was significantly elevated by Cd treatment, and this elevation was blocked by genistein, a protein tyrosine kinase inhibitor. In summary, the present results suggest that Cd stimulates the expression of ICAM-1 in bEnd.3 cells, via NF-kappaB activation that is mediated by the tyrosine phosphorylation of IkappaBalpha.
MeSH terms
AnimalsBrain/blood supply/*metabolismCadmium/*pharmacologyCell LineCerebrovascular Circulation/physiologyDose-Response Relationship, DrugEndothelium, Vascular/*metabolismGene Expression Regulation/drug effectsIntercellular Adhesion Molecule-1/*metabolismMiceMicrocirculation/*metabolismNF-kappa B/*metabolismTranscriptional Activation/drug effects
DOI
10.1016/j.bbrc.2004.05.218
PMID
15240131
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
문, 창현이, 수환백, 은주정, 이숙
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