Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons

John P. Kilkus, Rajendra Goswami, Sylvia A. Dawson, Fernando D. Testai, Eugeny V. Berdyshev, Xianlin Han, Glyn Dawson

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1745-1757
Number of pages13
JournalJournal of Neurochemistry
Volume106
Issue number4
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

Sphingomyelins
Oligodendroglia
Neurons
Sphingomyelin Phosphodiesterase
Oligodendroglioma
Rats
Cell death
Transfection
Cell Death
Cells
Cell Line
Sphingolipids
Palmitates
Ceramides
Neuroblastoma
Labeling
N-4-nitrobenzo-2-oxa-1,3-diazoleaminocaproyl sphingosylphosphorylcholine
Homeostasis
phosphatidylcholine-ceramide phosphocholine transferase

Keywords

  • Embryonic chick neurons
  • Fluorescent NBD-sphingolipids
  • Neonatal rat hippocampal neurons
  • Neonatal rat oligodendrocytes
  • Neurotumor cell lines
  • Sphingomyelin synthase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Kilkus, J. P., Goswami, R., Dawson, S. A., Testai, F. D., Berdyshev, E. V., Han, X., & Dawson, G. (2008). Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons. Journal of Neurochemistry, 106(4), 1745-1757. https://doi.org/10.1111/j.1471-4159.2008.05490.x

Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons. / Kilkus, John P.; Goswami, Rajendra; Dawson, Sylvia A.; Testai, Fernando D.; Berdyshev, Eugeny V.; Han, Xianlin; Dawson, Glyn.

In: Journal of Neurochemistry, Vol. 106, No. 4, 01.08.2008, p. 1745-1757.

Research output: Contribution to journalArticle

Kilkus, John P. ; Goswami, Rajendra ; Dawson, Sylvia A. ; Testai, Fernando D. ; Berdyshev, Eugeny V. ; Han, Xianlin ; Dawson, Glyn. / Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 4. pp. 1745-1757.
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