Differential inhibition of radiation-induced apoptosis.
Differential inhibition of radiation-induced apoptosis.
复制标题
辐射诱导的细胞凋亡的差异抑制。
DOI：
10.1002/stem.5530150708
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Fuks,Z
中科院分区：
文献类型：
--
作者：
Haimovitz-Friedman,A;Kolesnick,RN;Fuks,Z
辐射杀死细胞最常见的机制是诱导DNA双链断裂，导致细胞增殖丧失。尽管在体外和体内实验系统中越来越多地发现细胞凋亡，但它仍然被普遍认为是一种罕见的辐射诱导细胞杀伤模式，与辐射的临床效果关系不大。本文将重点讨论影响辐照下哺乳动物细胞凋亡结果的促凋亡和抗凋亡信号。特别是，我们将集中在鞘磷脂/神经酰胺信号转导途径，这是参与启动应激诱导的凋亡在各种正常和肿瘤细胞。我们还将讨论鞘磷脂/神经酰胺途径和构成抗凋亡途径的蛋白激酶C途径之间的串扰，以及在辐射暴露后增加凋亡细胞比例的药理学调节的潜力。
The most common mechanism by which radiation kills cells is the induction of DNA double-strand breaks that results in the loss of cell proliferation. Even though apoptosis is increasingly identified in experimental systems in vitro and in vivo, it is still generally regarded as a rare mode of radiation-induced cell kill with minor relevance for the clinical effects of radiation. This review will focus on pro- and antiapoptotic signaling that affects the apoptotic outcome in irradiated mammalian cells. In particular, we will concentrate on the sphingomyelin/ceramide signal transduction pathway which is involved in initiation of stress-induced apoptosis in a variety of normal and neoplastic cells. We will also discuss the crosstalk between the sphingomyelin/ceramide pathway and the protein kinase C pathway which constitutes an antiapoptotic pathway, and the potential for pharmacological modulation to increase the fraction of apoptotic cells undergoing apoptosis after radiation exposure.