Host: The Japanese Society of Toxicology
Epidemiological studies have indicated that cadmium is a risk factor for atherosclerosis. Previously, we reported that CHSY1, an elongation enzyme of dermatan sulfate chains that contributes to the formation of lipid plaques, is induced by cadmium exposure in cultured vascular endothelial cells. The purpose of this study is to investigate the involvement of CHSY1 on the cytotoxicity of cadmium in vascular endothelial cells. Confluent cultures of bovine aortic endothelial cells were transfected with CHSY1 overexpression vector or siRNA and then exposed to cadmium. The cytotoxicity of cadmium was inversely correlated with the expression level of CHSY1. Since cadmium cytotoxicity in cultured endothelial cells is characterized by the formation of de-endothelialized space associated with cell detachment and CHSY1 has been reported to be involved in epithelial-mesenchymal transition (EMT), a process that epithelial cells lose cell-cell adhesion and gain migratory properties, we analyzed the gene expression of EMT marker molecules that affect cell adhesion. A mesenchymal marker N-cadherin and an epithelial marker VE-cadherin were both induced by cadmium. Furthermore, the induction of N-cadherin was markedly suppressed in CHSY1 knock-downed cells, and cadmium cytotoxicity was enhanced by repression of N-cadherin expression. Although the direct interrelationship between cadmium cytotoxicity and EMT is not certain, this study showed that cadmium-induced CHSY1 exacerbates cadmium cytotoxicity and that N-cadherin, whose expression is upregulated with increased CHSY1, reduces the cytotoxicity by cadmium in vascular endothelial cells.
