Hyperpolarized 13 C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging
Open Access
- 31 October 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (46), 18606-18611
- https://doi.org/10.1073/pnas.1106920108
Abstract
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 [1-13C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized 13C spectroscopy. In murine models, hyperpolarized [1-13C] DHA was rapidly converted to [1-13C] 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 [1-13C] 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.Keywords
This publication has 49 references indexed in Scilit:
- Multi-band frequency encoding method for metabolic imaging with hyperpolarized [1-13C]pyruvateJournal of Magnetic Resonance, 2011
- Nox2 redox signaling maintains essential cell populations in the brainNature Chemical Biology, 2010
- Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studiesMagnetic Resonance in Medicine, 2010
- Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivoJournal of Magnetic Resonance, 2010
- Hyperpolarized [2-13C]-Fructose: A Hemiketal DNP Substrate for In Vivo Metabolic ImagingJournal of the American Chemical Society, 2009
- Silibinin Feeding Alters the Metabolic Profile in TRAMP Prostatic Tumors: 1H-NMRS–Based Metabolomics StudyCancer Research, 2009
- Fast multiecho balanced SSFP metabolite mapping of 1H and hyperpolarized 13C compoundsMagnetic Resonance Materials in Physics, Biology and Medicine, 2009
- Generation of hyperpolarized substrates by secondary labeling with [1,1- 13 C] acetic anhydrideProceedings of the National Academy of Sciences of the United States of America, 2009
- Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic productsJournal of Magnetic Resonance, 2008
- Effect of ascorbic acid on neurochemical, behavioral, and physiological systems mediated by catecholaminesLife Sciences, 1979