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Application of exogenous ceramide to cultured rat spinal motoneurons promotes survival or death by regulation of apoptosis depending on its concentrations
Author(s) -
Irie Fumitoshi,
Hirabayashi Yoshio
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19981115)54:4<475::aid-jnr5>3.0.co;2-p
Subject(s) - programmed cell death , ceramide , apoptosis , sphingomyelin , biology , intracellular , endogeny , microbiology and biotechnology , sphingosine , cell , biochemistry , membrane , receptor
The membrane lipid ceramide (Cer) has been shown to be involved in the survival and dendritic growth of cerebellar Purkinje cells and hippocampal neurons. We examined the effects of Cer on isolated rat spinal motoneurons. Basal neuronal cell death due to apoptosis occurs under these culture conditions. This cell death was prevented by treatment with 2.5 μM of D‐ erythro ‐N‐hexsanoylsphingosine (C 6 ‐Cer), a cell‐permeable analogue, and the surviving cell number was increased approximately 1.6‐fold compared with the control cell number on 5 days in vitro (DIV). Application of the same amount of C 6 ‐Cer improved axonal elongation. Conversely, addition of 10 μM of C 6 ‐Cer led all motoneurons to apoptotic cell death by 2DIV. A stereo isomer, threo ‐C 6 ‐Cer, which is not metabolized to C 6 ‐glucosylceramide, also promoted survival, death, and axonal growth in the same manners as C 6 ‐Cer. However, C 6 ‐dihydro‐Cer, a biologically inactive analogue, had no effects on survival or death, indicating that the presence of a double bond in the sphingosine base is essential for its activity. In addition, treatment with bacterial sphingomyelinase, which generates endogenous Cer, increases motoneuron survival and axonal growth. These observations suggest that Cer, but not its metabolites, regulates survival and development of spinal motoneurons, depending on its intracellular concentration. J. Neurosci. Res. 54:475–485, 1998. © 1998 Wiley‐Liss, Inc.