Ceramide mediates tumor necrosis factor effects on P450-aromatase activity in cultured granulosa cells.
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.
Santana
P
P
Departamento de Bioquímica y Biologia Molecular, Universidad de Las Palmas de Gran Canaria, School of Medicine, Spain.
Llanes
L
L
Hernandez
I
I
Gallardo
G
G
Quintana
J
J
Gonzalez
J
J
Estevez
F
F
Ruiz de Galarreta
C
C
Fanjul
L F
LF
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*
D002518:Ceramides; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D010767:Phosphorylcholine; D012694:Serine; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D002794:Choline