CERAMIDE CAN INDUCE CELL-DEATH IN SENSORY NEURONS, WHEREAS CERAMIDE ANALOGS AND SPHINGOSINE PROMOTE SURVIVAL

Ceramide has been shown to induce apoptosis in leukaemic cells and som e other cell types, but there are few data on its role in neuronal cel ls. We investigated the effect of ceramide and its analogues in cultur ed sensory neurons from neonatal mice. These cells undergo apoptosis i n the absence of neurotrophins. Treatment with ceramide or its analogu es increased survival, both in the presence and absence of NGF, Sphing osine treatment also increased survival. in the presence of the cerami dase inhibitor N-oleoyl ethanolamine, which blocks conversion of ceram ide to sphingosine, the addition of natural ceramide-induced cell deat h, even in the presence of nerve growth factor (NGF). N-oleoyl ethanol amine did not cause cell death by itself. N-oleoyl ethanolamine did no t alter the response to ceramide analogues, indicating that they were not ceramidase substrates. These results indicate that, in sensory neu rons, exogenous ceramide is converted to sphingosine, which promotes c ell survival. When conversion is blocked by ceramidase inhibition, exo genous ceramide causes cell death, presumably due to the high levels o f ceramide itself The ceramide analogues all mimicked the effect of sp hingosine rather than ceramide, casting serious doubt on their validit y as models of ceramide action. Ceramide analogues could prevent neuro nal death even in the combined presence of N-oleoyl ethanolamine and n atural ceramide. Surprisingly, dihydro Ca-ceramide, which is frequentl y used as a control for Ca-ceramide, had the same effect as ceramide a nalogues. J. Neurosci. Res. 54:206-213, 1998. (C) 1998 Wiley-Liss, Inc .