使用超极化碳-13磁共振对心脏中丙酮酸脱氢酶通量进行体内评估。

In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance.

作者信息

Schroeder Marie A, Cochlin Lowri E, Heather Lisa C, Clarke Kieran, Radda George K, Tyler Damian J

机构信息

Cardiac Metabolism Research Group, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.

出版信息

Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12051-6. doi: 10.1073/pnas.0805953105. Epub 2008 Aug 8.

DOI:10.1073/pnas.0805953105

PMID:18689683

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2515222/

Abstract

The advent of hyperpolarized (13)C magnetic resonance (MR) has provided new potential for the real-time visualization of in vivo metabolic processes. The aim of this work was to use hyperpolarized [1-(13)C]pyruvate as a metabolic tracer to assess noninvasively the flux through the mitochondrial enzyme complex pyruvate dehydrogenase (PDH) in the rat heart, by measuring the production of bicarbonate (H(13)CO(3)(-)), a byproduct of the PDH-catalyzed conversion of [1-(13)C]pyruvate to acetyl-CoA. By noninvasively observing a 74% decrease in H(13)CO(3)(-) production in fasted rats compared with fed controls, we have demonstrated that hyperpolarized (13)C MR is sensitive to physiological perturbations in PDH flux. Further, we evaluated the ability of the hyperpolarized (13)C MR technique to monitor disease progression by examining PDH flux before and 5 days after streptozotocin induction of type 1 diabetes. We detected decreased H(13)CO(3)(-) production with the onset of diabetes that correlated with disease severity. These observations were supported by in vitro investigations of PDH activity as reported in the literature and provided evidence that flux through the PDH enzyme complex can be monitored noninvasively, in vivo, by using hyperpolarized (13)C MR.

摘要

超极化（13）C磁共振（MR）的出现为体内代谢过程的实时可视化提供了新的潜力。这项工作的目的是使用超极化的[1-（13）C]丙酮酸作为代谢示踪剂，通过测量碳酸氢盐（H（13）CO（3）-）的产生来无创评估大鼠心脏中线粒体酶复合物丙酮酸脱氢酶（PDH）的通量，H（13）CO（3）-是PDH催化[1-（13）C]丙酮酸转化为乙酰辅酶A的副产物。通过无创观察，与喂食对照相比，禁食大鼠中H（13）CO（3）-的产生减少了74%，我们证明了超极化（13）C MR对PDH通量的生理扰动敏感。此外，我们通过在链脲佐菌素诱导1型糖尿病之前和之后5天检查PDH通量，评估了超极化（13）C MR技术监测疾病进展的能力。我们检测到糖尿病发作时H（13）CO（3）-的产生减少，这与疾病严重程度相关。这些观察结果得到了文献中报道的PDH活性的体外研究的支持，并提供了证据表明可以使用超极化（13）C MR在体内无创监测通过PDH酶复合物的通量。