Department of Chemistry, University of California, Berkeley, CA 94720.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
Proc Natl Acad Sci U S A. 2017 Nov 28;114(48):12669-12674. doi: 10.1073/pnas.1708747114. Epub 2017 Nov 14.
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 Fe with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe 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.
铁是所有生物体必需的金属元素，但铁的体内平衡被破坏，特别是不稳定形式的铁可能会导致氧化应激，这与从感染到癌症到神经退行性疾病等各种疾病有关。铁缺乏也是全世界最常见的营养缺乏症之一。为了深入研究健康和疾病状态下的铁，我们现在报告了笼状铁萤光素-1（ICL-1）的合成和特性，这是一种生物发光探针，可在活体动物中对不稳定铁池（LIP）进行纵向监测。ICL-1 利用生物启发的内过氧化物触发机制释放 d-氨基萤光素，用于基于选择性反应的铁检测，具有金属和氧化态特异性。该探针可检测活细胞和经历铁缺乏或过载的小鼠中不稳定铁水平的生理变化。ICL-1 在全身性细菌感染模型中的应用表明，感染组织中铁的积累增加，伴随着转录变化，这与铁摄取和保留的增加一致。在活体动物中评估铁状态的能力为研究铁代谢对生理和病理的贡献提供了一种强大的技术。
