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质子照射后小鼠大脑中差异氧化应激基因表达谱。

Differential oxidative stress gene expression profile in mouse brain after proton exposure.

机构信息

Molecular Toxicology Laboratory, Center for Biotechnology & Biomedical Sciences, Department of Biology, Norfolk State University, Norfolk, VA 23504, USA.

出版信息

In Vitro Cell Dev Biol Anim. 2010 Sep;46(8):718-25. doi: 10.1007/s11626-010-9330-2. Epub 2010 Jul 7.

Abstract

Radiation is known to potentially interfere with cellular functions at all levels of cell organization. The radiation-induced stress response is very complex and involves altered expression of many genes. Identification of specific genes may allow the determination of pathways important in radiation responses. Although several radiation-related research have been studied extensively, the molecular and cellular processes affected by proton exposure remain poorly understood. Our earlier reports have shown that proton radiation induces reactive oxygen species (ROS) formation and lipid peroxidation and inhibits antioxidants, superoxide dismutase, and glutathione. Therefore, in this present study, we used quantitative real-time reverse transcription polymerase chain reaction approach and showed the modulation of several genes including oxidative stress, antioxidants defense mechanism, ROS metabolism, and oxygen transporters related genes expression in 2-Gy proton-exposed mouse brain. Literature evidences suggest that change in oxidants and antioxidants levels induce DNA damage, followed by cell death. In conclusion, changes in the gene profile of mouse brain after proton irradiation are complex and the exposed cells might undergo programmed cell death through alteration of genes responsible for oxidative stress signaling mechanism.

摘要

辐射已知可能会在细胞组织的各个层面干扰细胞功能。辐射诱导的应激反应非常复杂,涉及许多基因表达的改变。鉴定特定的基因可能有助于确定在辐射反应中重要的途径。尽管已经对几项与辐射相关的研究进行了广泛研究,但质子暴露所影响的分子和细胞过程仍知之甚少。我们之前的报告表明,质子辐射会诱导活性氧(ROS)的形成和脂质过氧化,并抑制抗氧化剂、超氧化物歧化酶和谷胱甘肽。因此,在本研究中,我们使用定量实时逆转录聚合酶链反应方法,显示了几种基因的表达模式的调节,包括氧化应激、抗氧化防御机制、ROS 代谢和与氧转运体相关的基因在 2Gy 质子暴露的小鼠大脑中的表达。文献证据表明,氧化剂和抗氧化剂水平的变化会导致 DNA 损伤,随后是细胞死亡。总之,质子辐照后小鼠大脑的基因谱变化是复杂的,暴露的细胞可能通过改变负责氧化应激信号机制的基因而经历程序性细胞死亡。

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