title: Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons.
abstract: Neurons (both primary cultures of 3-day rat hippocampal neurons and embryonic chick neurons) rapidly converted exogenous NBD-sphingomyelin (SM) to NBD-Cer but only slowly converted NBD-Cer to NBD-SM. This was confirmed by demonstrating low in vitro sphingomyelin synthase (SMS) and high sphingomyelinase (SMase) activity in neurons. Similar results were observed in a human neuroblastoma cell line (LA-N-5). In contrast, primary cultures of 3-day-old rat oligodendrocytes only slowly converted NBD-SM to NBD-Cer but rapidly converted NBD-Cer to NBD-SM. This difference was confirmed by high in vitro SMS and low SMase activity in neonatal rat oligodendrocytes. Similar results were observed in a human oligodendroglioma cell line. Mass-Spectrometric analyses confirmed that neurons had a low SM/Cer ratio of (1.5 : 1) whereas oligodendroglia had a high SM/Cer ratio (9 : 1). Differences were also confirmed by [(3)H]palmitate-labeling of ceramide, which was higher in neurons compared with oligodendrocytes. Stable transfection of human oligodendroglioma cells with neutral SMase, which enhanced the conversion of NBD-SM to NBD-Cer and increased cell death, whereas transfection with SMS1 or SMS2 enhanced conversion of NBD-Cer to NBD-SM and was somewhat protective against cell death. Thus, SMS rather than SMases may be more important for sphingolipid homeostasis in oligodendrocytes, whereas the reverse may be true for neurons.
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, Illinois, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Kilkus
authors.forename: Rajendra
authors.initials: R
authors.lastname: Goswami
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Dawson
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Testai
authors.forename: Eugeny V
authors.initials: EV
authors.lastname: Berdyshev
authors.forename: Xianlin
authors.initials: X
authors.lastname: Han
authors.forename: Glyn
authors.initials: G
authors.lastname: Dawson
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology; D002642:Chick Embryo; D002645:Chickens; D006801:Humans; D008660:Metabolism / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013109:Sphingomyelins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology
chemical_list: D002518:Ceramides; C041065:N-4-nitrobenzo-2-oxa-1,3-diazoleaminocaproyl sphingosylphosphorylcholine; D013109:Sphingomyelins; D009327:4-Chloro-7-nitrobenzofurazan