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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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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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CHOp THER ApY INDUCED MITOCHONDRIAL REDOX STATE ALTERATION IN NON-HODGKIN'S LYMpHOMA XENOGRAFTS

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Journal of Innovative Optical Health Sciences 2013年第2期6卷 29-35页

作者： H.N.XU H.ZHAO T.A.MIR S.C.LEE M.FENG R.CHOE J.D.GLICKSON L.Z.LI Department of Radiology University of pennsylvania PhiladelphiaPAUSA Britton Chance Laboratory of Redox Imaging Johnson Research Foundation Department of Biochemistry and Biophysics University of pennsylvania PhiladelphiaPAUSA Biostatistics and Data Management Core The Children's Hospital of philadelphia(CHOp) PhiladelphiaPAUSA Department of Biomedical Engineering University of Rochester RochesterNYUSA Abramson Cancer Center University of pennsylvania PhiladelphiaPAUSA Institute of Translational Medicine and Therapeutics University of pennsylvania PhiladelphiaPAUSA

We are interested in investigating whether cancer therapy may alter the mitochondrial redox state in cancer cells to inhibit their growth and *** redox state can be imaged by the redox scanner that collects the fuorescence signals from both the oxidized-fAavoproteins(Fp)and the reduced form of nicotinamide adenine dinucleotide(NADH)in snap frozen tissues and has been previously employed to study tumor aggressiveness and treatment ***,with the redox scanner we investigated the effects of chemotherapy on mouse xenografts of a human diffuse large *** lymphoma cell line(DLCL2).The mice were treated with CHOp therapy,i.e,cyclophosphamide(C)+hydroxydoxorubicin(H)+Oncovin(O)+prednisone(p)with CHO administration on day 1 and prednisone administration on days *** Fp content of the treated group was significantly decreased(p=0.033)on day 5,and the mitochondrial redox state of the treated group was slightly more reduced than that of the control group(p=0.048).The decrease of the Fp heterogeneity(measured by the mean st andard deviation)had a border-line statistical significance(p=0.071).The result suggests that the mitochondrial metabolism of lymphoma cells was slightly suppressed and the lymphomas became less aggressive after the CHOp therapy.

关键词： NA DH flavoprotein DLCL2 therapeutic effect tumor metabolism

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