Divergent role of ceramide generated by exogenous sphingomyelinases on NF-kappa B activation and apoptosis in human colon HT-29 cells.
This study examined the role of ceramide generated by exogenous sphingomyelinases (SMases) on transcription nuclear factor-kappa B (NF-kappa B) activation and apoptosis in human colon epithelial HT-29 cells. Exogenous neutral (N) and acidic (A) SMase activated NF-kappa B with different kinetics, accounting for the diverse pattern of DNA binding of NF-kappa B complexes activated by tumor necrosis factor-alpha (TNF). NSMase activated predominantly RelA/p52 and RelA/p50 dimers within 30 min, while ASMase activated the p50/p50 homodimer by 20 h. The predominant activation of RelA-containing kappa B complexes by TNF or NSMase paralleled the induction of interleukin-8. HT-29 cells were sensitive to ASMase and TNF but resistant to NSMase. However, the apoptotic potential of NSMase was masked by NF-kappa B, as its prior inactivation sensitized HT-29 cells to NSMase. Thus, the generation of ceramide by exogenous SMases participates differentially in inflammation and apoptosis.
Liver Unit, Instituto de Malalties Digestives, Hospital Clinic i Provincial, Instituto Investigaciones Biomédicas August Pi Suñer, C/Villarroel 170, Barcelona 08036, Spain.
Anna
A
Colell
Olga
O
Coll
Montse
M
Mari
José C
JC
Fernández-Checa
Carmen
C
García-Ruiz
D017209:Apoptosis / Q000502:physiology*; D002518:Ceramides / Q000502:physiology*; D003110:Colonic Neoplasms; D019281:Dimerization; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002518:Ceramides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013108:Sphingomyelin Phosphodiesterase