title: Ceramide selectively inhibits apoptosis-associated events in NGF-deprived sympathetic neurons.
abstract: Ceramide manifests both neurotoxic and neuroprotective properties depending on the experimental system. Ito and Horigome previously reported that ceramide delays apoptosis in a classic model of developmental programmed cell death, i.e. sympathetic neurons undergoing NGF deprivation.1 Here, we investigated the actions of ceramide upon the biochemical and genetic changes that occur in NGF deprived neurons. We correlate ceramide's neuroprotective actions with the ability of ceramide to antagonize NGF deprivation-induced oxidative stress and c-jun induction, both of which contribute to apoptosis in this model. However, ceramide did not block NGF deprivation-induced declines in RNA and protein synthesis, suggesting that ceramide does not slow all apoptosis-related events. Overall, these results are significant in that they show that ceramide acts early in the death cascade to antagonize two events necessary for NGF-deprivation induced neuronal apoptosis. Moreover, these results dissociate declines in neuronal function, i.e. macromolecular synthesis, from the neuronal death cascade.
authors.affiliation: Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, KY 40536, USA.
authors.forename: P
authors.initials: P
authors.lastname: Nair
authors.forename: S P
authors.initials: SP
authors.lastname: Tammariello
authors.forename: S
authors.initials: S
authors.lastname: Estus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D004336:Drug Antagonism; D005786:Gene Expression Regulation / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D006801:Humans; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018384:Oxidative Stress; D013564:Sympathetic Nervous System / Q000473:pathology* / Q000502:physiology*
chemical_list: D002518:Ceramides; D020932:Nerve Growth Factor