title: Ceramide mediates tumor necrosis factor effects on P450-aromatase activity in cultured granulosa cells.
abstract: In [3H]serine-labelled granulosa cells treatment with TNF alpha (10 ng/ml) resulted in a transient decrease in cellular [3H]sphingomyelin and generation of [3H]ceramide that remained elevated 60 min later. In cells labelled with [methyl-14C]choline, TNF alpha induced a similar reduction in [14C]sphingomyelin content that was accompanied by a sustained elevation in [14C]phosphorylcholine levels. In FSH-primed cells, TNF alpha inhibited P450-AROM activity in a dose-dependent manner, an effect that was also observed in cells treated with bacterial sphingomyelinase (SMase 0.003-0.3 U/ml) or increasing concentrations (0.1-10 microM) of N-acetylsphingosine (C2-cer) a membrane-permeable analogue of ceramide. These results support the notion that sphingomyelin degradation to a bioeffector molecule ceramide, may be an early event involved in TNF alpha-induced signal transduction in granulosa cells.
authors.affiliation: Departamento de Bioquímica y Biologia Molecular, Universidad de Las Palmas de Gran Canaria, School of Medicine, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Santana
authors.forename: L
authors.initials: L
authors.lastname: Llanes
authors.forename: I
authors.initials: I
authors.lastname: Hernandez
authors.forename: G
authors.initials: G
authors.lastname: Gallardo
authors.forename: J
authors.initials: J
authors.lastname: Quintana
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez
authors.forename: F
authors.initials: F
authors.lastname: Estevez
authors.forename: C
authors.initials: C
authors.lastname: Ruiz de Galarreta
authors.forename: L F
authors.initials: LF
authors.lastname: Fanjul
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010767:Phosphorylcholine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002518:Ceramides; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D010767:Phosphorylcholine; D012694:Serine; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D002794:Choline