       Document 0298
 DOCN  M9460298
 TI    Dissociation of endogenous cellular ceramide from NF-kappa B activation.
 DT    9404
 AU    Betts JC; Agranoff AB; Nabel GJ; Shayman JA; Department of Internal
       Medicine, University of Michigan, Ann; Arbor 48109-0676.
 SO    J Biol Chem. 1994 Mar 18;269(11):8455-8. Unique Identifier : AIDSLINE
       MED/94179231
 AB    The participation of cell ceramide in tumor necrosis factor
       (TNF)-alpha-stimulated NF-kappa B activation in Jurkat T cells and HL-60
       cells was studied. TNF-alpha readily stimulated NF-kappa B activity in
       both cell lines as assayed by electrophoretic mobility shift assay and
       the use of a human immunodeficiency virus-chloramphenicol
       acetyltransferase reporter construct. However, TNF-alpha stimulation did
       not increase cell ceramide levels in either cell line. The exogenous
       addition of a short chain ceramide, N-acetylsphingosine, to Jurkat cells
       had no effect on NF-kappa B activity. When Jurkat T cells were exposed
       to the glucosylceramide synthase inhibitor,
       1-phenyl-2-decanoylamino-3-morpholino-1-propanol, endogenous ceramide
       levels increased 4-fold. The increase in ceramide, however, did not
       result in NF-kappa B activation nor did it potentiate TNF-alpha or
       phorbol ester-stimulated activity. We conclude that TNF-alpha-induced
       NF-kappa B activation occurs in Jurkat and HL-60 cell lines that do not
       demonstrate an increase in TNF-alpha-induced ceramide. Increasing
       ceramide levels by the addition of short chain ceramides or the use of a
       glucosylceramide synthase inhibitor can be dissociated from activation
       of NF-kappa B by TNF-alpha.
 DE    Antineoplastic Agents/PHARMACOLOGY  Cell Line  Ceramides/*METABOLISM
       Chloramphenicol Acetyltransferase/BIOSYNTHESIS/METABOLISM  Genetic
       Vectors  Human  HIV  Kinetics  Leukemia, Promyelocytic, Acute  Leukemia,
       T-Cell  Morpholines/PHARMACOLOGY  NF-kappa B/*METABOLISM  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't,
       P.H.S.  Tetradecanoylphorbol Acetate/PHARMACOLOGY  Time Factors
       Transfection  Tumor Cells, Cultured  Tumor Necrosis Factor/*PHARMACOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

