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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter
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In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter

机译：化学选择性生物发光报告基因在小鼠肿瘤模型中产生过氧化氢的体内成像

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摘要

Living organisms produce hydrogen peroxide (H_2O_2) to kill invading pathogens and for cellular signaling, but aberrant generation of this reactive oxygen species is a hallmark of oxidative stress and inflammation in aging, injury, and disease. The effects of H_2O_2 on the overall health of living animals remain elusive, in part owing to a dearth of methods for studying this transient small molecule in vivo. Here we report the design, synthesis, and in vivo applications of Peroxy Caged Luciferin-1 (PCL-1), a chemoselective bioluminescent probe for the real-time detection of H_2O_2 within living animals. PCL-1 is a boronic acid-caged firefly luciferin molecule that selectively reacts with H_2O_2 to release firefly luciferin, which triggers a bioluminescent response in the presence of firefly luciferase. The high sensitivity and selectivity of PCL-1 for H_2O_2, combined with the favorable properties of bioluminescence for in vivo imaging, afford a unique technology for real-time detection of basal levels of H_2O_2 generated in healthy, living mice. Moreover, we demonstrate the efficacy of PCL-1 for monitoring physiological fluctuations in H_2O_2 levels by directly imaging elevations in H_2O_2 within testosterone-stimulated tumor xenografts in vivo. The ability to chemoselectively monitor H_2O_2 fluxes in real time in living animals offers opportunities to dissect H_2O_2's disparate contributions to health, aging, and disease.
机译：活生物体产生过氧化氢（H_2O_2）以杀死入侵的病原体并用于细胞信号传导，但是这种活性氧物种的异常产生是衰老，伤害和疾病中氧化应激和炎症的标志。 H_2O_2对活体动物整体健康的影响仍然难以捉摸，部分原因是缺乏体内研究这种瞬时小分子的方法。在这里，我们报告过氧笼式萤光素1（PCL-1）的设计，合成和体内应用，这是一种化学选择性生物发光探针，用于实时检测活体动物体内的H_2O_2。 PCL-1是一种硼酸笼蔽的萤火虫荧光素分子，可选择性地与H_2O_2反应释放萤火虫荧光素，萤火虫荧光素酶的存在会触发生物发光反应。 PCL-1对H_2O_2的高灵敏度和选择性，以及用于体内成像的生物发光的良好特性，为实时检测健康活体小鼠体内H_2O_2的基础水平提供了独特的技术。此外，我们证明了PCL-1通过直接成像体内睾丸激素刺激的肿瘤异种移植物中H_2O_2的升高来监测H_2O_2水平的生理波动的功效。实时化学选择性监测活体动物中H_2O_2通量的能力提供了剖析H_2O_2对健康，衰老和疾病的不同贡献的机会。

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    Genevieve C. Van de Bittner; Elena A. Dubikovskaya; Carolyn R. Bertozzi; Christopher J. Chang;

  • 作者单位

    Department of ChemistryUniversity of California, Berkeley,CA 94720;

    Department of ChemistryUniversity of California, Berkeley,CA 94720,;

    Department of ChemistryUniversity of California, Berkeley,CA 94720,Howard Hughes Medical InstituteUniversity of California, Berkeley,CA 94720 Department of Molecular and Cell Biology, University of California, Berkeley,CA 94720,The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;

    Department of ChemistryUniversity of California, Berkeley,CA 94720,Howard Hughes Medical InstituteUniversity of California, Berkeley,CA 94720;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cancer; molecular imaging; redox biology;

    机译：癌症;分子成像;氧化还原生物学;

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