Sawai H, Okazaki T, Domae N
Department of Internal Medicine, Faculty of Medicine, Kyoto University.
Nihon Rinsho. 1996 Jul;54(7):1803-8.
Ceramide, the backbone of sphingolipids, is now recognized as an intracellular signal mediator of various cellular responses including cell differentiation and apoptosis. Tumor necrosis factor-alpha, anti-Fas antibody, anticancer drugs, radiation or heat shock induce apoptosis through generation of ceramide by activation of sphingomyelinase or ceramide synthase. The mechanism by which ceramide mediates apoptosis is unclear. We have found that ceramide induces the transcription of c-jun gene and increases the DNA binding activity of transcription factor AP-1 in human myelogenous leukemia HL-60 cells, and that activation of c-jun/AP-1 by ceramide(presumably through activation of Jun N-terminal kinase/stress-activated protein kinase) may be involved in the signaling pathway leading to apoptosis.
神经酰胺作为鞘脂类的核心成分，目前被认为是多种细胞反应（包括细胞分化和凋亡）的细胞内信号介质。肿瘤坏死因子-α、抗Fas抗体、抗癌药物、辐射或热休克可通过鞘磷脂酶或神经酰胺合酶的激活产生神经酰胺来诱导凋亡。神经酰胺介导凋亡的机制尚不清楚。我们发现神经酰胺可诱导人髓性白血病HL-60细胞中c-jun基因的转录，并增加转录因子AP-1的DNA结合活性，并且神经酰胺对c-jun/AP-1的激活（可能是通过Jun N端激酶/应激激活蛋白激酶的激活）可能参与了导致凋亡的信号通路。
