VIRAL-PROTEINS E1B19K AND P35 PROTECT SYMPATHETIC NEURONS FROM CELL-DEATH INDUCED BY NGF DEPRIVATION

To study molecular mechanisms underlying neuronal cell death, we have used sympathetic neurons from superior cervical ganglia which undergo programmed cell death when deprived of nerve growth factor. These neur ons have been microinjected with expression vectors containing cDNAs e ncoding selected proteins to test their regulatory influence over cell death. Using this procedure, we have shown previously that sympatheti c neurons can be protected from NGF deprivation by the protooncogene B cl-2. We now report that the E1B19K protein from adenovirus and the p3 5 protein from baculovirus also rescue neurons. Other adenoviral prote ins, E1A and E1B55K, have no effect on neuronal survival. E1B55K, know n to block apoptosis mediated by p53 in proliferative cells, failed to rescue sympathetic neurons suggesting that p53 is not involved in neu ronal death induced by NGF deprivation. E1B19K and p35 were also coinj ected with Bcl-Xs which blocks Bcl-2 function in lymphoid cells. Altho ugh Bcl-Xs blocked the ability of Bcl-2 to rescue neurons, it had no e ffect on survival that was dependent upon expression of E1B19K or p35.