N-acylated serinol is a novel ceramide mimic inducing apoptosis in neuroblastoma cells

Erhard Bieberich, Takahisa Kawaguchi, Robert K. Yu

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

A novel structural analog of ceramide was synthesized by N-acylation of serinol (2-amino-1,3-propanediol) and studied for its effects on glycolipid biosynthesis and cell differentiation of neuroblastoma cells. Incubation with N-palmitoylated serinol (C16-serinol) increased the concentration of endogenous ceramide by 50-80% and caused apoptosis in rapidly dividing low density cells but not in confluent cells. Cell death was not suppressed by simultaneous incubation with phorbol ester, known to antagonize ceramide- induced apoptosis by activation of protein kinase C (PKC). Purification of potential target proteins of C16-serinol was achieved by affinity chromatography of a protein preparation from rat brain on immobilized C16- serinol. A gel activity assay revealed that the eluate from C16-serinol- Sepharose contained three serine/threonine-specific protein kinases with molecular masses of 50, 70, and 95 kDa. The 70-kDa protein was immunostained on a Western blot using a PKCζ-specific antibody. The purified PKCζ could be activated directly by C16-serinol in an in vitro phosphorylation assay. Induction of apoptosis in neuroblastoma cells was suppressed by inhibition of PKCζ with Go 6983. Our overall results indicate that apoptosis in neuroblastoma cells induced by C16-serinol was at least partially mediated by activation of PKCζ on condition of ongoing cell division. N-Acylated serinols may thus be useful for induction of apoptosis in mitotic cells and may be of therapeutic potential for treatment of cancer in the nervous system.

Original languageEnglish (US)
Pages (from-to)177-181
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number1
DOIs
StatePublished - Jan 7 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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