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γ射线照射后进行甲基供体饥饿处理对p53蛋白谱的修饰。

Modification of p53 protein profile by gamma irradiation followed by methyl donor starvation.

作者信息

Batra Vipen, Kesavan Vellappan, Mishra Kaushala P

机构信息

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Modular Laboratories, Room No. 3-47-S, Mumbai-400 085, India.

出版信息

Mol Cell Biochem. 2006 Dec;293(1-2):15-21. doi: 10.1007/s11010-006-1170-8. Epub 2006 Jun 9.

Abstract

The possible beneficial radio-protective effects of one-carbon transfer agents namely folate, choline and methionine have been the subject of extensive investigation. Ionizing radiation is known to extensively damage the DNA. One-carbon transfer agents have been proposed to have important role in context of DNA repair via their role in purine and thymidylate synthesis and in DNA methylation. Sufficient dietary availability of one-carbon transfer agents therefore, might have ability to modify radiation effects. In present study modifications in level of tumor suppressor protein p53 by gamma irradiation followed by methyl donor starvation was observed. Experiments showed an increase in nuclear and cytoplasmic p53 protein concentration in liver, spleen and thymus. The overall rise in the level of p53 protein in liver was found to be less than that in spleen and thymus. Moreover significant heterogeneity in the basal level of expression of the p53 protein in liver, spleen and thymus was observed as the level of p53 protein in spleen and thymus was found to be 7-8 fold more than that in liver. Results indicated that radiation stress followed by methyl donor starvation could significantly induce p53 protein in spleen and thymus where there was a dramatic accumulation of p53 following irradiation, while in other tissues, particularly the liver, no such dramatic response was seen. Folate contribution of intestinal bacteria was found to influence p53 protein levels. Our observations indicated a prominent role played by the methyl donors in protecting the cell against harmful effects of ionizing radiation.

摘要

一碳转移剂,即叶酸、胆碱和蛋氨酸,可能具有的有益辐射防护作用一直是广泛研究的主题。已知电离辐射会广泛损伤DNA。有人提出一碳转移剂通过在嘌呤和胸苷酸合成以及DNA甲基化中的作用,在DNA修复过程中发挥重要作用。因此,一碳转移剂在饮食中的充足供应可能有能力改变辐射效应。在本研究中,观察到γ射线照射后接着甲基供体饥饿对肿瘤抑制蛋白p53水平的影响。实验表明,肝脏、脾脏和胸腺中核和细胞质p53蛋白浓度增加。发现肝脏中p53蛋白水平的总体升高低于脾脏和胸腺。此外,观察到肝脏、脾脏和胸腺中p53蛋白基础表达水平存在显著异质性,因为脾脏和胸腺中p53蛋白水平比肝脏中高7至8倍。结果表明,辐射应激后接着甲基供体饥饿可显著诱导脾脏和胸腺中的p53蛋白,照射后p53在这些器官中大量积累,而在其他组织,特别是肝脏中,未观察到这种显著反应。发现肠道细菌的叶酸贡献会影响p53蛋白水平。我们的观察结果表明甲基供体在保护细胞免受电离辐射有害影响方面发挥着重要作用。

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