Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells.
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.
Jeong
Euy-Myoung
EM
Department of Physiology, School of Medicine, Ajou University, Suwon 442-749, Republic of Korea.
Moon
Chang-Hyun
CH
Kim
Chan-Sik
CS
Lee
Soo Hwan
SH
Baik
Eun Joo
EJ
Moon
Chang Kiu
CK
Jung
Yi-Sook
YS
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology*; D002460:Cell Line; D002560:Cerebrovascular Circulation / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051379:Mice; D008833:Microcirculation / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D016328:NF-kappa B; D002104:Cadmium; D018799:Intercellular Adhesion Molecule-1