RRC ID 12228
Author Sawai H, Okazaki T, Yamamoto H, Okano H, Takeda Y, Tashima M, Sawada H, Okuma M, Ishikura H, Umehara H.
Title Requirement of AP-1 for ceramide-induced apoptosis in human leukemia HL-60 cells.
Journal J Biol Chem
Abstract Ceramide has emerged as a novel lipid mediator in cell proliferation, differentiation, and apoptosis. In this work, we demonstrate that the levels of c-jun mRNA, c-Jun protein, and DNA binding activity of a nuclear transcription factor AP-1 to 12-o-tetradecanoylphorbol 13-acetate responsive elements all increased following treatment with the cell-permeable ceramide, N-acetylsphingosine in human leukemia HL-60 cells. N-Acetylsphingosine (1-10 microM) increased the levels of c-jun mRNA in a dose-dependent manner, and maximal expression was achieved 1 h after treatment. Increase of c-jun expression treated with 5 microM N-acetyldihydrosphingosine, which could not induce apoptosis, was one third of that with 5 microM N-acetylsphingosine. Ceramide-induced growth inhibition and DNA fragmentation were both prevented by treatment with curcumin, 1,7-bis[4-hydroxy-3-methoxy-phenyl]-1,6-heptadiene-3,5-dione (an inhibitor of AP-1 activation), or antisense oligonucleotides for c-jun. These results suggest that the transcription factor AP-1 is critical for apoptosis in HL-60 cells and that an intracellular sphingolipid mediator, ceramide, modulates a signal transduction inducing apoptosis through AP-1 activation.
Volume 270(45)
Pages 27326-31
Published 1995-11-10
DOI 10.1074/jbc.270.45.27326
PMID 7592995
MeSH Apoptosis / drug effects* Apoptosis / genetics Apoptosis / physiology* Base Sequence Curcumin / pharmacology DNA, Neoplasm / genetics DNA, Neoplasm / metabolism Gene Expression / drug effects Genes, jun Humans Leukemia / genetics Leukemia / metabolism* Leukemia / pathology* Molecular Sequence Data Oligonucleotides, Antisense / genetics Oligonucleotides, Antisense / pharmacology Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction Sphingosine / analogs & derivatives* Sphingosine / pharmacology Transcription Factor AP-1 / metabolism* Tumor Cells, Cultured
IF 4.106
Times Cited 182
DNA material pBS rcjun-1 (RDB01130)