Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts.
Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts.
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DOI：
10.1093/jrr/rru078
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发表时间：
2015-01
影响因子：
2
通讯作者：
Sakai A
中科院分区：
文献类型：
--
作者：
Tsuyama N;Mizuno H;Katafuchi A;Abe Y;Kurosu Y;Yoshida M;Kamiya K;Sakai A
电离辐射（IR）诱导细胞应激反应，如信号转导、基因表达、蛋白质修饰和影响细胞行为的代谢物变化。我们分析了经x射线照射的人eb病毒转化的B淋巴母细胞样细胞和正常成纤维细胞，用液相色谱-质谱法（LC-MS）寻找合适的ir反应标记物。质谱主成分分析表明，与培养时间的影响相比，红外诱导变化的峰所占比例相对较小。提取了数十个被IR上调或下调的峰作为候选IR标记物。通过将模拟处理组与10 h后恢复的100 mgy照射组进行比较，确定了ir变化峰，结果表明B淋巴母细胞样细胞中参与核苷合成的代谢物增加，一些酰基肉碱水平降低。一些峰值变化高达20mgy，表明这些细胞中存在红外敏感信号转导/代谢控制机制。另一方面，我们在不同来源的成纤维细胞中没有发现共同的ir变化峰。这些数据表明，即使在低剂量反应中，细胞表型特异性途径也存在，并且可以决定细胞行为。
Ionizing radiation (IR) induces cellular stress responses, such as signal transduction, gene expression, protein modification, and metabolite change that affect cellular behavior. We analyzed X-irradiated human Epstein-Barr virus-transformed B lymphoblastoid cells and normal fibroblasts to search for metabolites that would be suitable IR-responsive markers by Liquid Chromotography–Mass spectrometry (LC–MS). Mass spectra, as analyzed with principal component analysis, showed that the proportion of peaks with IR-induced change was relatively small compared with the influence of culture time. Dozens of peaks that had either been upregulated or downregulated by IR were extracted as candidate IR markers. The IR-changed peaks were identified by comparing mock-treated groups to 100 mGy-irradiated groups that had recovered after 10 h, and the results indicated that the metabolites involved in nucleoside synthesis increased and that some acylcarnitine levels decreased in B lymphoblastoids. Some peaks changed by as much as 20 mGy, indicating the presence of an IR-sensitive signal transduction/metabolism control mechanism in these cells. On the other hand, we could not find common IR-changed peaks in fibroblasts of different origin. These data suggest that cell phenotype-specific pathways exist, even in low-dose responses, and could determine cell behavior.