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J Biol Chem, Vol. 275, Issue 1, 177-181, January 7, 2000
From the Department of Biochemistry and Molecular Biochemistry,
Medical College of Virginia Campus of Virginia Commonwealth University,
Richmond, Virginia 23298-0614
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 PKC
N-Acylated Serinol Is a Novel Ceramide Mimic
Inducing Apoptosis in Neuroblastoma Cells*
,
-specific antibody.
The purified PKC could be activated directly by C16-serinol in an
in vitro phosphorylation assay. Induction of apoptosis in neuroblastoma cells was suppressed by inhibition of PKC with Gö 6983. Our overall results indicate that apoptosis in
neuroblastoma cells induced by C16-serinol was at least partially
mediated by activation of PKC 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.
*
This study was supported by United States Public Health
Service Grant NS 11853 and an A. D. Williams grant.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Biochemistry
and Molecular Biophysics, Medical College of Virginia Campus of
Virginia Commonwealth University, 1101 E. Marshall St., P. O. Box
980614, Richmond, VA 23298. Tel.: 804-828-9217; Fax: 804-828-1473; E-mail: ebieberi@hsc.vcu.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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