Temporal expression of hypoxia-regulated genes is associated with early changes in redox status in irradiated lung.
Temporal expression of hypoxia-regulated genes is associated with early changes in redox status in irradiated lung.
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DOI：
10.1016/j.freeradbiomed.2012.04.014
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发表时间：
2012-07-15
影响因子：
7.4
通讯作者：
Vujaskovic, Zeljko
中科院分区：
文献类型：
--
作者：
Jackson, Isabel L.;Zhang, Xiuwu;Hadley, Caroline;Rabbani, Zahid N.;Zhang, Yu;Marks, Sam;Vujaskovic, Zeljko
辐射暴露后正常肺组织毒性的发展是由于电离事件时细胞信号和通讯的多重变化引起的。严重肺损伤发生前，组织缺氧和慢性氧化应激。我们之前的研究表明，辐射后24小时给予AEOL10150（一种强效催化抗氧化剂）可以减轻或预防衰弱性肺损伤的发展。这表明缺氧介导的信号通路可能在晚期辐射损伤中起作用，但确切的机制尚不清楚。本研究的目的是评估辐照小鼠肺中缺氧相关基因的时间表达变化，并确定AEOL10150是否会改变这些基因的表达。利用聚焦寡核苷酸阵列建立了AEOL10150处理或不处理的假辐照或辐照小鼠肺组织的缺氧相关基因表达特征。RT-PCR进一步验证了结果。44个与代谢、细胞生长、凋亡、炎症、氧化应激和细胞外基质合成相关的基因在辐射后表达上调。其中31个基因的高表达在AEOL10150处理的动物中被减弱，这表明一些低氧相关基因的表达受到辐射后氧化应激早期发展的调节。本研究发现的基因可以深入了解缺氧信号在放射性肺损伤中的作用，提出新的治疗靶点，并为AEOL10150提供肺放射保护的机制提供线索。
The development of normal lung tissue toxicity after radiation exposure results from multiple changes in cell signaling and communication initiated at the time of the ionizing event. The onset of gross pulmonary injury is preceded by tissue hypoxia and chronic oxidative stress. We have previously shown development of debilitating lung injury can be mitigated or prevented by administration of AEOL10150, a potent catalytic antioxidant, 24 hours after radiation. This suggests that hypoxia-mediated signaling pathways may play a role in late radiation injury, but the exact mechanism remains unclear. The purpose of this study was to evaluate changes in the temporal expression of hypoxia-associated genes in irradiated mouse lung and determine whether AEOL10150 alters expression of these genes. A focused oligo array was used to establish a hypoxia-associated gene expression signature for lung tissue from sham-irradiated or irradiated mice treated with or without AEOL10150. Results were further verified by RT-PCR. 44 genes associated with metabolism, cell growth, apoptosis, inflammation, oxidative stress and extracellular matrix synthesis were upregulated after radiation. Elevated expression of 31 of these genes was attenuated in animals treated with AEOL10150, suggesting that expression of a number of hypoxia-associated genes are regulated by early development of oxidative stress after radiation. Genes identified herein could provide insight into the role of hypoxic signaling in radiation lung injury, suggesting novel therapeutic targets, as well as clues to the mechanism by which AEOL10150 confers pulmonary radioprotection.
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影响因子：
7.4
作者：
Gauter-Fleckenstein, Benjamin;Fleckenstein, Katharina;Owzar, Kouros;Jiang, Chen;Reboucas, Julio S.;Batinic-Haberle, Ines;Vujaskovic, Zeljko
通讯作者：
Vujaskovic, Zeljko
影响因子：
4.6
作者：
McCourtie, Anton S.;Farivar, Alexander S.;Mulligan, Michael S.
通讯作者：
Mulligan, Michael S.
DOI：
10.1016/j.ijrobp.2006.12.056
发表时间：
2007-05-01
影响因子：
7
作者：
Fleckenstein, Katharina;Zgonjanin, Larisa;Vujaskovic, Zeljko
通讯作者：
Vujaskovic, Zeljko
影响因子：
3.4
作者：
Jackson, Isabel L.;Vujaskovic, Zeljko;Down, Julian D.
通讯作者：
Down, Julian D.
影响因子：
--
作者：
BarcellosHoff, MH;Dix, TA
通讯作者：
Dix, TA