Department of Radiology and Biomedical Imaging, University of California San Francisco, 1700 4th Street, Byers Hall 203, San Francisco, CA 94158, USA.
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18606-11. doi: 10.1073/pnas.1106920108. Epub 2011 Oct 31.
Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-(13)C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized (13)C spectroscopy. In murine models, hyperpolarized [1-(13)C] DHA was rapidly converted to [1-(13)C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-(13)C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS.
氧化还原（redox）化学参与正常和异常的细胞功能，在诸如昼夜节律和神经传递等多样化的过程中发挥作用。细胞内的氧化还原通过涉及 NADPH、谷胱甘肽 (GSH) 和维生素 C 及其相应氧化对应物的偶联反应来维持。除了作为酶辅因子发挥作用外，这些还原剂在处理活性氧 (ROS) 方面具有关键作用，ROS 是氧化代谢的有毒产物，被认为是衰老、神经退行性疾病和缺血/再灌注损伤的罪魁祸首。尽管氧化还原与人类疾病之间存在很强的关系，但体内探究氧化还原对的方法有限。在这里，我们报告了[1-(13)C]脱氢抗坏血酸（DHA）的开发，DHA 是维生素 C 的氧化形式，可用作体内成像的内源性氧化还原传感器，使用极化 (13)C 光谱。在小鼠模型中，极化[1-(13)C]DHA 迅速在肝脏、肾脏和大脑以及转基因前列腺癌小鼠的肿瘤内转化为[1-(13)C]维生素 C。这一结果与先前描述的 DHA/维生素 C 氧化还原对一致，并表明极化[1-(13)C]DHA 在表征包括 GSH 在内的关键细胞内还原剂浓度方面具有作用。更广泛地说，这些发现表明这种新的氧化还原传感器在确定正常和异常组织对 ROS 的易感性方面具有预后作用。
