NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes aswell as in the regulation of embryonic development and aging,To fluorimetrically sssthemitochondrial redox state,Dr.Chance and c...NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes aswell as in the regulation of embryonic development and aging,To fluorimetrically sssthemitochondrial redox state,Dr.Chance and co-workers measured the fluorescence of NADH andoxidized flavoproteins(Fp)including favin-adenine-dinucleotide(FAD)and demonstrated theirratio(i.e.the redox ratio)is a sensitive indicator of the mitochondrial redox states.,The Chanceredox sca mer was built to simult aneously measure NADH and Fp in tisue at submilimeter scalein 3D using the freeze-trap protocol.This paper summarizes our recent research experience,development and new applications of the redox scanning technique in collaboration with Dr.Chance beginning in 2005.Dr.Chance initiated or actively involved in many of the projectsduring the last several years of his life.We advanced the redox scanning technigue by measuringthe nominal concentrations(in reference to the frozen solution standards)of the endogenousfuorescent analy tes,i.e.,[NADH]and[rp]to quantify the redox ratios in various biologicaltissues.The advancement has enabled us to identify an array of the redox indices as quantitativeimaging,biomarkers(including[NADH],[Fp],[Fp]/[NADH]+[Fp],[NADH]/[Fp],and theirstandard deviations)for studying some important biological questions on cancer and normaltsue metabolism.We found that the redox indices were asociated or changed with(NADH)tumorigenesis(cancer versus non-cancer of human breast tisue biopsies);(2)tumor metastaticpotential;(3)tumor glucose uptake;(4)tumor p53 stat us;(5)PI3K pathway activation in pre-malignant tissue;(6)therapeutic ffects on tumors;(7)embryonic stem cell diferentiation;(8)the heart under fasting,Together,our work demonstrated that the tisue redox indices obtainedfrom the redox scanning technique may provide usefil information about tisue met abolism and physiology status in normal and diseased tissues.The Chance redox scanner and other redoximaging techniques may have wide-ranging potential applications in many fields,such as cancer,diabetes,developmental process,mitochondrial diseases,neurodegenerative diseases,and aging.展开更多
基金made possible by the financial support of National Institute of Health(R01 CA155348(L.Z.Li))。
文摘NAD+/NADH redox state has been implicated in many diseases such as cancer and diabetes aswell as in the regulation of embryonic development and aging,To fluorimetrically sssthemitochondrial redox state,Dr.Chance and co-workers measured the fluorescence of NADH andoxidized flavoproteins(Fp)including favin-adenine-dinucleotide(FAD)and demonstrated theirratio(i.e.the redox ratio)is a sensitive indicator of the mitochondrial redox states.,The Chanceredox sca mer was built to simult aneously measure NADH and Fp in tisue at submilimeter scalein 3D using the freeze-trap protocol.This paper summarizes our recent research experience,development and new applications of the redox scanning technique in collaboration with Dr.Chance beginning in 2005.Dr.Chance initiated or actively involved in many of the projectsduring the last several years of his life.We advanced the redox scanning technigue by measuringthe nominal concentrations(in reference to the frozen solution standards)of the endogenousfuorescent analy tes,i.e.,[NADH]and[rp]to quantify the redox ratios in various biologicaltissues.The advancement has enabled us to identify an array of the redox indices as quantitativeimaging,biomarkers(including[NADH],[Fp],[Fp]/[NADH]+[Fp],[NADH]/[Fp],and theirstandard deviations)for studying some important biological questions on cancer and normaltsue metabolism.We found that the redox indices were asociated or changed with(NADH)tumorigenesis(cancer versus non-cancer of human breast tisue biopsies);(2)tumor metastaticpotential;(3)tumor glucose uptake;(4)tumor p53 stat us;(5)PI3K pathway activation in pre-malignant tissue;(6)therapeutic ffects on tumors;(7)embryonic stem cell diferentiation;(8)the heart under fasting,Together,our work demonstrated that the tisue redox indices obtainedfrom the redox scanning technique may provide usefil information about tisue met abolism and physiology status in normal and diseased tissues.The Chance redox scanner and other redoximaging techniques may have wide-ranging potential applications in many fields,such as cancer,diabetes,developmental process,mitochondrial diseases,neurodegenerative diseases,and aging.
