Ceramide signaling in apoptosis.
Ceramide signaling in apoptosis.
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DOI：
10.1093/oxfordjournals.bmb.a011629
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发表时间：
1996-11
影响因子：
6.7
通讯作者：
A. Haimovitz-Friedman;R. Kolesnick;Z. Fuks
中科院分区：
文献类型：
--
作者：
A. Haimovitz-Friedman;R. Kolesnick;Z. Fuks
鞘磷脂途径是一种普遍存在的、进化上保守的信号传导系统，由质膜磷脂鞘磷脂水解产生神经酰胺而引发。神经酰胺作为第二信使激活凋亡级联反应。不同的细胞因子受体和环境压力利用神经酰胺信号细胞凋亡。在一些细胞系统中，神经酰胺连接到应激活化蛋白激酶（SAPK）/c-jun激酶（JNK）级联以信号细胞凋亡。神经鞘磷脂途径参与细胞凋亡信号传导受到抗细胞凋亡控制机制的严格调节，并且促细胞凋亡和抗细胞凋亡系统之间的平衡决定了体外和体内细胞凋亡反应的幅度。本文综述了神经酰胺介导的细胞凋亡的已知元件和分子排序以及调节其表达的抗凋亡机制。了解神经酰胺介导的细胞凋亡中涉及的促凋亡和抗凋亡信号传导及其协调功能的模式，可能会为具有临床应用潜力的药理学干预提供机会。
The sphingomyelin pathway is a ubiquitous, evolutionarily conserved signaling system initiated by hydrolysis of the plasma membrane phospholipid sphingomyelin to generate ceramide. Ceramide acts as a second messenger in activating the apoptotic cascade. Diverse cytokine receptors and environmental stresses utilize ceramide to signal apoptosis. In several cell systems ceramide links to the stress-activated protein kinase (SAPK)/c-jun kinase (JNK) cascade to signal apoptosis. The engagement of the sphingomyelin pathway in signaling apoptosis is tightly regulated by anti-apoptotic control mechanisms, and the balance between pro- and anti-apoptotic systems determines the magnitude of the apoptotic response in vitro and in vivo. This review describes the known elements and molecular ordering of ceramide-mediated apoptosis and the anti-apoptotic mechanisms that regulate its expression. Understanding of pro- and anti-apoptotic signaling involved in ceramide-mediated apoptosis and the modes of their co-ordinated function may yield opportunities for pharmacological interventions with potential for clinical applications.