Near total body exposure to high-dose ionizing radiation results in organ-specific sequelae, including acute radiation syndromes and delayed effects of acute radiation exposure. Among these sequelae are acute kidney injury and chronic kidney injury. Reports that neither oxidative stress nor inflammation are dominant mechanisms defining radiation nephropathy inspired an unbiased, discovery-based proteomic interrogation in order to identify mechanistic pathways of injury. We quantitatively profiled the proteome of kidney from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Kidney was analyzed by liquid chromatography-tandem mass spectrometry. Out of the 3,432 unique proteins that were identified, we found that 265 proteins showed significant and consistent responses across at least three time points post-irradiation, of which 230 proteins showed strong upregulation while 35 proteins showed downregulation. Bioinformatics analysis revealed significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. These data will be useful for a greater understanding of the molecular mechanisms of injury in well-characterized animal models of partial body irradiation with minimal bone marrow sparing. These data may be potentially useful in the future development of medical countermeasures.

中文翻译：

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非人类灵长类动物肾脏在少量保留骨髓的局部辐射后的急性蛋白质组学变化。

近全身暴露于高剂量电离辐射会导致器官特异性后遗症，包括急性辐射综合征和急性辐射暴露的延迟效应。这些后遗症包括急性肾损伤和慢性肾损伤。关于氧化应激和炎症都不是定义放射性肾病的主要机制的报道激发了一种公正的、基于发现的蛋白质组学研究，以识别损伤的机制途径。我们在 3 周的时间段内，在 12 Gy 部分身体照射和 2.5% 的骨髓保留后，定量分析了非人类灵长类动物的肾脏蛋白质组。通过液相色谱-串联质谱分析肾脏。在已鉴定的 3,432 种独特蛋白质中，我们发现 265 种蛋白质在辐照后至少三个时间点显示出显着且一致的反应，其中 230 种蛋白质表现出强烈的上调，而 35 种蛋白质表现出下调。生物信息学分析揭示了高剂量照射后显着的通路和上游调节剂扰动，并揭示了辐射损伤的潜在机制。这些数据将有助于更好地了解在充分表征的部分身体照射动物模型中损伤的分子机制，而骨髓保留最少。这些数据可能对未来医学对策的发展有用。生物信息学分析揭示了高剂量照射后显着的通路和上游调节剂扰动，并揭示了辐射损伤的潜在机制。这些数据将有助于更好地了解在充分表征的部分身体照射动物模型中损伤的分子机制，而骨髓保留最少。这些数据可能对未来医学对策的发展有用。生物信息学分析揭示了高剂量照射后显着的通路和上游调节剂扰动，并揭示了辐射损伤的潜在机制。这些数据将有助于更好地理解部分身体照射的充分表征的动物模型中损伤的分子机制，并且骨髓保留最少。这些数据可能对未来医学对策的发展有用。