In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection
In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection
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DOI：
10.1073/pnas.1708747114
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发表时间：
2017-11-28
影响因子：
11.1
通讯作者：
Chang, Christopher J.
中科院分区：
文献类型：
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作者：
Aron, Allegra T.;Heffern, Marie C.;Chang, Christopher J.
铁是所有生物体的必需金属，但其体内平衡的破坏，尤其是可能导致氧化应激的不稳定形式，与感染、癌症和神经退行性疾病等疾病有关。缺铁也是全世界最常见的营养缺乏症之一。为了推进健康和疾病状态下铁的研究，我们现在报告铁笼荧光素-1 (ICL-1) 的合成和表征，这是一种生物发光探针，能够纵向监测活体动物中的不稳定铁池 (LIP)。 ICL-1 利用仿生内过氧化物触发器释放 D-氨基荧光素，用于基于金属和氧化态特异性的 Fe2+ 选择性反应性检测。该探针可以检测活细胞和缺铁或铁过载小鼠中不稳定 Fe2+ 水平的生理变化。 ICL-1 在全身细菌感染模型中的应用揭示了感染组织中铁积累的增加，伴随着与铁获取和保留增加一致的转录变化。评估活体动物铁状态的能力为研究铁代谢对生理学和病理学的贡献提供了强大的技术。
Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release D-aminoluciferin for selective reactivity-based detection of Fe2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe2+ levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.