Zhu Xiao-Hong, Lu Ming, Lee Byeong-Yeul, Ugurbil Kamil, Chen Wei
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN 55455.
Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2876-81. doi: 10.1073/pnas.1417921112. Epub 2015 Feb 17.
NAD is an essential metabolite that exists in NAD(+) or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD(+)/NADH redox state and modulating cellular signaling processes through the activity of the NAD(+)-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD(+) and NADH contents and the NAD(+)/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.
NAD是一种必需的代谢物，在所有活细胞中以NAD(+)或NADH的形式存在。尽管它在通过NAD(+)/NADH氧化还原状态调节线粒体能量产生以及通过NAD(+)依赖性酶的活性调节细胞信号传导过程中起着关键作用，但定量细胞内NAD含量和氧化还原状态的方法仅限于少数体外或离体测定，这些方法不适用于研究活的大脑或器官。在此，我们提出一种基于磁共振（MR）的体内NAD测定方法，该方法使用高场MR扫描仪，能够无创地评估完整人脑中NAD(+)和NADH的含量以及NAD(+)/NADH氧化还原状态。据我们所知，这项研究的结果首次揭示了健康志愿者大脑中的细胞NAD浓度和氧化还原状态。此外，该研究还揭示了健康人脑中细胞内NADH随年龄增长而增加，以及NAD(+)、总NAD含量和NAD(+)/NADH氧化还原电位随年龄增长而降低。总体研究结果不仅为正常衰老过程中伴随的线粒体功能下降和NAD稳态改变提供了直接证据，还阐明了这种新的NAD测定方法在无创研究正常和患病人类大脑或其他器官原位细胞内NAD代谢和氧化还原状态方面的优点和潜力。
