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Ceramide Initiates NF Kappa B‐Mediated Caspase Activation In Neuronal Apoptosis
Author(s) -
Gill JS,
Windebank AJ
Publication year - 2001
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2001.01008-11.x
Subject(s) - ceramide , microbiology and biotechnology , apoptosis , programmed cell death , intracellular , lipid signaling , nfkb1 , biology , ceramide synthase , nf κb , cyclin d1 , signal transduction , chemistry , transcription factor , cell cycle , biochemistry , receptor , gene
The objective of the present study was to evaluate the role of ceramide in mediating apoptosis of dorsal root ganglion neurons induced by either nerve growth factor withdrawal or treatment with the chemotherapeutic agents suramin and cisplatin. Measurement of ceramide accumulation by mass spectrometry and the diacylglycerol kinase assay revealed elevation of intracellular ceramide only in suramin treated cultures. Ceramide‐mediated neuronal cell death was inhibited by the caspase inhibitor zVAD.fmk. In these experimental models, ceramide accumulation mediated activation and nuclear translocation of the transcription factor NF kappa B and cyclin D1 protein expression. Specific inhibition of NF kappa B using a molecular decoy strategy resulted in increased cell viability accompanied by diminished caspase activity and cyclin D1 expression. Inhibition of NF kappa B did not alter intracellular ceramide levels. Our study suggests that ceramide generation occurs upstream of NF kappa B activation, cell cycle reentry, and caspase activation in the neuronal death pathway.