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3D imaging of the mitochondrial redox state of rathearts under normal and fasting conditions

Journal of Innovative Optical Health Sciences 2014年第2期7卷 60-69页

作者： He N.Xu Rong Zhou lily moon Min Feng Lin Z.Li Department of Radiology Universityof PennsyluaniaPhilade lphia PA 19104USA Briton Chance Laboratory of Redor Imaging Johnson Research Foundation Department of Biochemistry and Biophysics University of Pennsyluania Philade lphiaPA 19104USA Institute of Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104USA

The heart requires continuous ATP availability that is generated in the *** using the cell culture and perfiused organ models have been carried out to investigate thebiochemistry in the mitochondria in response to a change in substrate supply,mitochondrialbioenergetics of heart under normal feed or fasting conditions has not been studied at the tissuelevel with a sub-millimeter spatial resolution either in vivo or er *** of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+couple acting as a central electron *** employed the Chance redox scanner thelow-temperat ure fluorescence scanner to image the three-dimensional(3D)spatial distribution of themitochondrial redox states in heart tissues of rats under normai feeding or an overnight star-vation for 14.5 *** consecutive sections of each heart were imaged to map three redoxindices,i.e,NADH,oxidized favoproteins Fp,including flavin adenine dinucleotide(FAD)andthe redox ratio NADH/*** imaging results revealed the micro-heterogeneity and the spatial distribution of these redox *** quantitative analysis showed that in the fasted hearts thestandard deviation of both NADH and Fp,ie.,SD NADH and SDFp,significantly decreasedwith a p value of 0.032 and 0.045,respectively,indicating that the hearts become relatively morehomogeneous after *** fasted hearts contained 28.6%less NADH(p=0.038).No *** change in Fp was foumnd(p=0.4).The NADH/Fp ratio decreased with a marginalP value(0.076).The decreased NADH im the fasted hearts is consistent with the cardiac celsreliance of fatty acids consumption for energy metabolism when glucose becomes *** o bservation of N ADH decrease induced by dietary restriction in the heart at tissuelevel has not been reported to our best *** Chance redox scanner demonstrated thefeasibility of 3D imaging of the mitochondrial redox st ate in the heart and

关键词： Mitochondion metabolism bioenergetics cardiomyocyte NADH flavoproteins Fp FAD caloric restriction food deprivation.

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REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX VIVO

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Journal of Innovative Optical Health Sciences 2013年第3期6卷 1-10页

作者： HE N.XU MIN FENG lily moon NATHAN DOLLOFF WAFIKEL-DEIRY LIN Z.LI Department of Radiology University of Pennsylvania PhiladelphiaPAUSA Britton Chance Laboratory of Redox Imaging Johnson Research Foundation Department of Biochemistry and Biophysics Perelman School of Medicine University of Pennsylvania PhiladelphiaPAUSA Department of Medicine Penn State Hershey Medical Center and Penn State College of MedicineHersheyPAUSA Hematology/Oncology Penn State Hershey Medical Center HersheyPAUSA Abramson Cancer Center University of Pennsylvania PhiladelphiaPAUSA Institute of Translational Medicine and Therapeutics University of Pennsylvania PhiladelphiaPAUSA

The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously *** has how p53 regulates mitochondial respi ration been measured at(deep)tissue level,presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration *** prior work demonstrated that the mito-chondrial redox state and its intnatumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models,with the more metastatic tumons exhi-bit ing localized negions of more oxidized redox *** the Chance redox scanner with an in-plane spatial resolution of 200 pm,we imaged the mitochondrial redox state of the wild-type p53 colon tumors(HCT116 p53 ut)and the p5-deleted colon tumors(HCT116 p53-/-)by cllcting the fuorescence si gnals of nicotinamide adenine dimucleotide(NA DH)and oxidized flavoproteins [Fp,including favin adenine dinucleotide(FAD)]from the mouse xenogmafts snap frozen at low *** results show that:(1)both tumor lines have significant degree of intratumor heterogeneity of the redox state,typically exhibiting a distinct bi modal distribution that either correlates with the spatial core-rim pattern or the“hot/oold”oxida tion-roduction patches;.(2)the p531-group is significantly more beterogencous in the mitochondrial redox state and has a more oxidized turmor core compared to the p53 wt group when the tunor sizes of the two groups are matched;(3)the tumor size dependence of the redox indices(such as Fp and Fp redox ratio)is significant in the p531-group with the larger ones being more oxidized and more hetero-geneous in their redox state,particularly more oxidized in the tumor central regions;(4)the H&E staining images of tumor soctions grossly correlate with the redox *** present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattem of the mitochon-drial redox state in colon cancer and

关键词： NADH favoprotein intratumor heterogeneity HCT116 p53 null necrotic

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应用强斯氧化还原扫描仪探测小鼠体内组织代谢状态空间分布

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中国医疗设备 2013年第6期28卷 1-6页

作者：孟丽丽孙楠楠李琳宾夕法尼亚大学佩雷尔曼医学院放射学系分子成像实验室美国宾州费城19104 宾夕法尼亚大学佩雷尔曼医学院生物化学和生物物理系强森研究基金会布立顿.强斯氧化还原成像实验室美国宾州费城19104

氧化还原状态能为癌症等多种疾病提供组织内与能量相关的生物过程和信号活动等方面的重要信息。强斯氧化还原扫描仪根据还原型烟酰胺腺嘌呤二核苷酸(NADH)和氧化型黄素蛋白(Fp,包括黄素腺嘌呤二核苷酸即FAD)的荧光信号建立组织内线粒体... 详细信息

氧化还原状态能为癌症等多种疾病提供组织内与能量相关的生物过程和信号活动等方面的重要信息。强斯氧化还原扫描仪根据还原型烟酰胺腺嘌呤二核苷酸(NADH)和氧化型黄素蛋白(Fp,包括黄素腺嘌呤二核苷酸即FAD)的荧光信号建立组织内线粒体氧化还原三维高清图像。本文阐述了强斯氧化还原扫描仪的基本原理和方法,分析了对正常和肿瘤组织的扫描结果,显示组织内氧化还原态空间分布的异质性,并对强斯氧化还原扫描仪在医学中的应用潜力进行初步的探讨。

关键词：强斯氧化还原扫描仪氧化黄素蛋白黄素腺嘌呤二核苷酸烟酰胺腺嘌呤二核苷酸氧化还原态氧化还原比组织异质性组织代谢

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