Exploring the link between ceramide and ionizing radiation
Exploring the link between ceramide and ionizing radiation
复制标题
DOI：
10.1007/s10719-014-9541-y
复制
发表时间：
2014-10-01
影响因子：
3
通讯作者：
Sonnino, Sandro
中科院分区：
文献类型：
--
作者：
Aureli, Massimo;Murdica, Valentina;Sonnino, Sandro
放射治疗的目的是用电离辐射消灭癌细胞;辐射后的肿瘤细胞死亡可由几种信号传导途径诱导，其中大多数是由于DNA损伤而触发的，DNA损伤是对辐射的主要和主要相关细胞反应。一些证据表明，神经酰胺，一个重要的传感器和/或不同的信号转导途径的效应，促进细胞周期停滞，死亡和分化，直接参与细胞对辐射的反应的分子机制。大多数研究强烈支持神经酰胺蓄积与辐射诱导的细胞死亡（主要是细胞凋亡）之间的直接关系;因此，确定导致神经酰胺形成的多种代谢途径的贡献及其代谢失调的原因是阐明神经酰胺介导的放射治疗信号传导的主要目标。在这篇综述中，我们总结了有关辐射诱导的细胞反应中导致神经酰胺积累的不同途径的现有知识，特别是涉及神经酰胺新生和分解代谢的酶的作用。重点放在神经酰胺生成激活后细胞照射的机制鞘脂分解，这一途径的功能相关性，和鞘糖脂糖水解酶作为电离辐射的直接目标的作用也进行了讨论。这些新的发现增加了一个更有吸引力的调查点，以更好地定义鞘脂代谢和放射治疗之间的复杂相互作用。
The aim of radiotherapy is to eradicate cancer cells with ionizing radiation; tumor cell death following irradiation can be induced by several signaling pathways, most of which are triggered as a consequence of DNA damage, the primary and major relevant cell response to radiation. Several lines of evidence demonstrated that ceramide, a crucial sensor and/or effector of different signalling pathways promoting cell cycle arrest, death and differentiation, is directly involved in the molecular mechanisms underlying cellular response to irradiation. Most of the studies strongly support a direct relationship between ceramide accumulation and radiation-induced cell death, mainly apoptosis; for this reason, defining the contribution of the multiple metabolic pathways leading to ceramide formation and the causes of its dysregulated metabolism represent the main goal in order to elucidate the ceramide-mediated signaling in radiotherapy. In this review, we summarize the current knowledge concerning the different routes leading to ceramide accumulation in radiation-induced cell response with particular regard to the role of the enzymes involved in both ceramide neogenesis and catabolism. Emphasis is placed on sphingolipid breakdown as mechanism of ceramide generation activated following cell irradiation; the functional relevance of this pathway, and the role of glycosphingolipid glycohydrolases as direct targets of ionizing radiation are also discussed. These new findings add a further attractive point of investigation to better define the complex interplay between sphingolipid metabolism and radiation therapy.