Neuronal and glial differentiation of neuroblastoma and glioma cells by Rho inhibitory bacterial exo-enzyme C3

Exoenzyme C3 (C3) produced by Clostridium botulinum type C and D strains specifically modifies the small GTP-binding protein Rho. It has been reported that C3 induces neuronal differentiation of the PC12 cell, an adrenergic cell line. In this study, the effects of C3 on a cholinergic cell line (NG108–15) and a glioma (C6) were examined for their differentiation. Treatment of NG108–15 cells and C6 glioma cells with C3 for 3 days induced neurite or process formation. Moreover, treatment by C3 increased the activities of acetylcholine esterase and choline acetyltransferase in NG108–15 cells, and 2′,3′-cyclic nucleotide 3′-phosphohydrolase in C6 cells. These results suggest that C3 induces neuronal differentiation of the cholinergic cell as well as the adrenergic cell, and also glial differentiation of the glioma cell.