Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.
Anticancer Agents Med Chem. 2012 May;12(4):340-63. doi: 10.2174/187152012800228661.
Programmed cell death, or apoptosis, is a complex process whereby eukaryotic cells react to physiologic or pathophysiologic stimuli by undergoing genetically programmed suicide. Programmed cell death involves many well-characterized signaling pathways including permeabilization of the mitochondrial outer membrane and activation of caspases. Other pathways, such as pro-apoptotic lipid signaling, are less understood despite many years of study. The sphingolipid ceramide has received considerable attention as a key regulator of programmed cell death, yet the mechanisms of its up-regulation and ability to control cell fate remain ill-defined. In this review, we will examine the connections between sphingolipid metabolism and programmed cell death with a focus on the role of de novo sphingolipid synthesis and sphingosine salvage in producing pro-apoptotic ceramide. We will also highlight the evidence supporting an increasingly complex role for ceramide in regulating apoptosis and provide a framework in which to ask new questions about the functions of this enigmatic lipid.
程序性细胞死亡，又称细胞凋亡，是真核细胞对生理或病理刺激做出反应的一种复杂过程，通过基因编程实现自杀。程序性细胞死亡涉及许多特征明确的信号通路，包括线粒体外膜的通透性和半胱天冬酶的激活。其他途径，如促凋亡脂质信号，尽管已经研究了很多年，但仍知之甚少。神经酰胺作为程序性细胞死亡的关键调节因子受到了相当多的关注，但其上调机制及其控制细胞命运的能力仍不明确。在这篇综述中，我们将探讨鞘脂代谢与程序性细胞死亡之间的联系，重点关注从头合成鞘脂和鞘氨醇回收在产生促凋亡神经酰胺中的作用。我们还将强调支持神经酰胺在调节细胞凋亡中发挥复杂作用的证据，并提供一个框架，以便提出关于这种神秘脂质功能的新问题。
