title: Protein kinase C inhibition induces apoptosis and ceramide production through activation of a neutral sphingomyelinase.
abstract: We report that WEHI-231 undergo apoptosis following exposure to the protein kinase C inhibitors chelerythrine chloride and calphostin C. Following the addition of chelerythrine or calphostin C to WEHI-231 cells, ceramide production increased over baseline levels with a concurrent decrease in sphingomyelin. More detailed examinations determined that the ceramide accumulation resulted from activation of neutral, but not acidic, sphingomyelinase. These results suggest an antagonistic relationship between protein kinase C activity and ceramide in the signaling events preceding apoptosis.
authors.affiliation: Department of Pathology, Division of Biological Sciences, University of Chicago, Illinois, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chmura
authors.forename: E
authors.initials: E
authors.lastname: Nodzenski
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: J
authors.initials: J
authors.lastname: Quintans
mesh_terms: D000470:Alkaloids; D017209:Apoptosis; D053119:Benzophenanthridines; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis*; D006868:Hydrolysis; D009281:Naphthalenes / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D002518:Ceramides; D009281:Naphthalenes; D010617:Phenanthridines; D013109:Sphingomyelins; C016299:chelerythrine; D011493:Protein Kinase C; D013108:Sphingomyelin Phosphodiesterase; C058819:calphostin C