Effects of Cadmium Chloride on Neurite Outgrowth and Gene Expression in Human Neuroblastoma NB-1 Cells

Abstract

Cadmium is a well-studied environmental toxicant. The neurotoxicity of cadmium is a concern, especially in the developing human brain, because it is thought that cadmium exerts long-term and irreversible effects. In the present study cadmium toxicity using human neuroblastoma NB-1 cells was investigated in relation to gene expression and subsequent neurite extension using cDNA macroarray and image analysis techniques. The neurite outgrowth in NB-1 cells was stimulated significantly by the presence of dibutyryl-cyclicAMP (db-cAMP) and by cadmium chloride at sublethal concentrations. Db-cAMP-stimulated neurite outgrowth was associated with a three-fold increased expression of axonal membrane protein growth-associated protein-43 (GAP-43), but cadmium chloride did not affect GAP-43 expression. Db-cAMP also increased dopamine β-hydroxylase gene expression eight-fold and down-regulated muscle/brain cAMP-dependent protein kinase inhibitor gene expression. However, cadmium chloride had no effect on gene expression except for that of metallothionein II (mtII) gene among 1764 genes analyzed. The results demonstrate that the increased neurite outgrowth with cadmium chloride is not associated with the same gene expression profile of that with db-cAMP.