Santana P, Llanes L, Hernandez I, Gallardo G, Quintana J, Gonzalez J, Estevez F, Ruiz de Galarreta C, Fanjul L F
Departamento de Bioquímica y Biologia Molecular, Universidad de Las Palmas de Gran Canaria, School of Medicine, Spain.
Endocrinology. 1995 May;136(5):2345-8. doi: 10.1210/endo.136.5.7720683.
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.
在用[3H]丝氨酸标记的颗粒细胞中，用肿瘤坏死因子α（10纳克/毫升）处理导致细胞内[3H]鞘磷脂短暂减少，并产生[3H]神经酰胺，60分钟后其水平仍保持升高。在用[甲基-14C]胆碱标记的细胞中，肿瘤坏死因子α诱导[14C]鞘磷脂含量出现类似降低，同时[14C]磷酸胆碱水平持续升高。在促卵泡激素预处理的细胞中，肿瘤坏死因子α以剂量依赖方式抑制P450-芳香化酶活性，在用细菌鞘磷脂酶（0.003 - 0.3单位/毫升）或浓度递增（0.1 - 10微摩尔）的N-乙酰鞘氨醇（C2-神经酰胺，神经酰胺的一种膜通透性类似物）处理的细胞中也观察到了这种效应。这些结果支持这样一种观点，即鞘磷脂降解为生物效应分子神经酰胺可能是颗粒细胞中肿瘤坏死因子α诱导信号转导的早期事件。
