The evaluation of the potential of botulinum C3 enzyme as an exogenous differentiation inducing factor to neurons

Botulinum C3 enzyme produced by Clostridium botulinum type C and D strains modifies Rho proteins. In a previous study, we observed that the LDH isozym e pattern of neurons treated with C3 enzyme was different from that induced with endogenous growth factor of neurons such as NGF [21]. This type of ch ange is considered to have an advantage in the medical use of C3 enzyme for neural disorder. To determine the functional similarity of C3-treated neur ons to control and NGF-treated neurons, we examined the responses of C3-tre ated neurons to various drugs, including some neurotransmitters, by measuri ng the rise of intracellular Ca ions into the neurons. The time course of t he rise of intracellular Ca ions induced by high concentration of potassium in the C3-treated neurons was similar to that in the NGF-treated neurons. The C3-treated neurons responded to glutamic acid, aspartic acid, kainic ac id, gamma-aminobutylic acid, muscarine and ACh with similar time courses an d magnitudes as the control neurons. These results suggest that the C3 enzy me induces the functional differentiation of neurons, and that C3 enzyme ha s the potential for the medical use as an exogenous differentiation-inducin g factor of neurons.