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

• Published in: Biochemical and biophysical research communications Vol. 320; no. 3; pp. 887 - 892
• Main Authors: Jeong, Euy-Myoung, Moon, Chang-Hyun, Kim, Chan-Sik, Lee, Soo Hwan, Baik, Eun Joo, Moon, Chang Kiu, Jung, Yi-Sook
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 30-07-2004
• Subjects: Brain microvessel endothelial cells; Cadmium; ICAM-1; IκBα; NF-κB activation; Tyrosine phosphorylation; Cadmium; NF-κB activation; ICAM-1; Brain microvessel endothelial cells; Tyrosine phosphorylation; IκBα
• DOI: 10.1016/j.bbrc.2004.05.218
• EISSN: 1090-2104
• ISSN: 0006-291X

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-κB inhibitor SN50. The treatment with Cd induced the translocation of NF-κB from cytosolic to membrane fraction and increased DNA binding activity of NF-κB, and this NF-κB activation was inhibited by SN50. Interestingly, Cd did not trigger the degradation of IκBα, suggesting that Cd-induced ICAM-1 expression is mediated through IκBα degradation-independent pathway. Instead, tyrosine phosphorylation of IκBα 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-κB activation that is mediated by the tyrosine phosphorylation of IκBα.