Specific toxicity of tunicamycin in induction of programmed cell death of sympathetic neurons

Tunicamycin belongs to a group of antibiotics which can cause severe a nd often fatal neurological malfunction in animals, commonly known as "annual ryegrass toxicity." At the cellular level, tunicamycin is a potent glycosylation inhibitor which is often used to elucidate the importance of glycosylation in protein functions. Earlier reports suggested that tunicamycin was able to interfere with the binding of nerve growth factor to its receptors. In this report, we showed that tunicamycin was able to kill sympathetic neurons in cultures. The mechanism of cell death was observed to be similar to that of "programmed cell death" in sympathetic neurons induced by nerve growth factor deprivation. Such tunicamycin-induced cell death could be prevented by the protein synthesis inhibitor cycloheximide, which was known to prevent the programmed cell death in sympathetic neurons. These results demonstrated that, in addition to the proven CNS neurotoxicity in animals, tunicamycin causes programmed cell death in peripheral (sympathetic) neurons.