Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons |
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Authors: | Kilkus John P Goswami Rajendra Dawson Sylvia A Testai Fernando D Berdyshev Eugeny V Han Xianlin Dawson Glyn |
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Institution: | Department of Pediatrics, University of Chicago, Chicago, Illinois, USA; Department of Neurology, University of Chicago, Chicago, Illinois, USA; Department of Medicine, University of Chicago, Chicago, Illinois, USA; Division of Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St Louis, Missouri, USA; Departments of Pediatrics, Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA |
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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 3H]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. |
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Keywords: | embryonic chick neurons fluorescent NBD-sphingolipids neonatal rat hippocampal neurons neonatal rat oligodendrocytes neurotumor cell lines sphingomyelin synthase |
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