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 im portance of glycosylation in protein functions. Earlier reports sugges ted that tunicamycin was able to interfere with the binding of nerve g rowth factor to its receptors. In this report, we showed that tunicamy cin was able to kill sympathetic neurons in cultures. The mechanism of cell death was observed to be similar to that of ''programmed cell de ath'' in sympathetic neurons induced by nerve growth factor deprivatio n. Such tunicamycin-induced cell death could be prevented by the prote in synthesis inhibitor cycloheximide, which was known to prevent the p rogrammed cell death in sympathetic neurons. These results demonstrate d that, in addition to the proven CNS neurotoxicity in animals, tunica mycin causes programmed cell death in peripheral (sympathetic) neurons . (C) 1996 Academic Press, Inc.