Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 320, Issue 3, Pages 887-892Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2004.05.218
Keywords
cadmium; ICAM-1; NF-kappa B activation; brain microvessel endothelial cells; tyrosine phosphorylation; I kappa B alpha
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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. (C) 2004 Elsevier Inc. All rights reserved.
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