Dynamic Optical Imaging of Metabolic and NADPH Oxidase-Derived Superoxide in Live Mouse Brain Using Fluorescence Lifetime Unmixing

Hall, D.; Han, Sung-Ho; Chepetan, Andre; Inui, Edny G; Rogers, Michael J.; Dugan, Laura L.

doi:10.1038/jcbfm.2011.143

Cited by 11 publications

(20 citation statements)

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“…To evaluate O2 .production in the kidney, 18week-aged db/db and db/m mice underwent administration of DHE for 16 hours prior to euthanasia at which time kidneys were harvested (6), at this point all unreacted DHE has been excreted (9). DHE oxidation signal was prominent in the kidney of db/m mice ( Fig.…”

Section: Diabetic Db/db Mice Have Reduced Renal Superoxide (O2 -) Prmentioning

confidence: 99%

“…Two major oxidation products of DHE are ethidium (E + ) and 2-hydroxyethidium (2-OH-E + ). Although, "in vitro" studies using highperformance liquid chromatography (HPLC) have suggested that the specific oxidation product of DHE by O2 .is 2-OH-E + (7,13,14), a recent report by Hall et al demonstrated the discrepancy between in vitro and in vivo results for DHE oxidation products (9). Using a novel in vivo live animal imaging method which utilized the difference of fluorescence lifetimes between the two DHE oxidation products (E + ; 6 ns, 2-OH-E + ; 12 ns), it was showed that the predominant oxidation product in vivo was E + , but not 2-OH-E + (9).…”

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confidence: 99%

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Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease

Miyamoto

Zhang

Hall

et al. 2020

Journal of Biological Chemistry

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Exposure to chronic hyperglycemia because of diabetes mellitus can lead to development and progression of diabetic kidney disease (DKD). We recently reported that reduced superoxide production is associated with mitochondrial dysfunction in the kidneys of mouse models of type 1 DKD. We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-derived metabolites in their urine. Here we examined renal superoxide production in a type 2 diabetes animal model, the db/db mouse, and the role of a mitochondrial protectant, MTP-131 (also called elamipretide, SS-31, or Bendavia) in restoring renal superoxide production and ameliorating DKD. We found that 18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2. Administration of MTP-131 significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling.

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Section: Diabetic Db/db Mice Have Reduced Renal Superoxide (O2 -) Prmentioning

confidence: 99%

mentioning

confidence: 99%

Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease

Miyamoto

Zhang

Hall

et al. 2020

Journal of Biological Chemistry

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“…; Hall et al . ), including hippocampal slices of mice (Haley et al . ) and rats (D'agostino et al .…”

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confidence: 99%

“…Dihydroethidium is a fluorescent dye that is oxidized by superoxide into the stable dihydroxy ethidium (DHE). Based on its ability to detect intracellular and extracellular superoxide, DHE is used for in vitro and in vivo analysis superoxide (Peshavariya et al 2007;Hall et al 2012), including hippocampal slices of mice and rats (D'agostino et al 2007).…”

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confidence: 99%

Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species

Villasana

Weber

Akinyeke

et al. 2016

Journal of Neurochemistry

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Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer’s disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following 56Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not wild-type, mice, PMA-treated hippocampal slices showed more DHE oxidation in sham-irradiated than irradiated mice and hippocampal HO-1 levels were higher in irradiated than sham-irradiated E4 mice.

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“…Hence, we expect that this implementation is well suited for a wide array of optical molecular applications that leverage lifetime sensing, such as multiplexed in vivo receptor engagement and/or high dimensional optical tomography based on structured light strategies 28 . The in vivo imaging protocols reported were conducted in about 14 minutes, and acquisition times from over ten minutes to hours are needed for the state-of-the-art commercial MFLI system, eXplore Optix, to scan a similar area of a mouse for only one wavelength [29][30][31] . However, the data acquisition time of our method can be considerably reduced if the spatial bases are optimized, less-dense temporal data sets are acquired, the fluorescence decay curve is temporally gated for an enhanced SNR or the spectral band integrated.…”

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confidence: 99%

Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging

Intes

2017

Wavelets and Sparsity XVII

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Spectrally resolved fluorescence lifetime imaging 1-3 and spatial multiplexing 1,4,5 have offered information content and collection-efficiency boosts in microscopy, but efficient implementations for macroscopic applications are still lacking. An imaging platform based on time-resolved structured light and hyperspectral single-pixel detection has been developed to perform quantitative macroscopic fluorescence lifetime imaging (MFLI) over a large field of view (FOV) and multiple spectral bands simultaneously. The system makes use of three digital micromirror device (DMD)-based spatial light modulators (SLMs) to generate spatial optical bases and reconstruct N by N images over 16 spectral channels with a time-resolved capability (~40 ps temporal resolution) using fewer than N 2 optical measurements. We demonstrate the potential of this new imaging platform by quantitatively imaging near-infrared (NIR) Förster resonance energy transfer (FRET) both in vitro and in vivo. The technique is well suited for quantitative hyperspectral lifetime imaging with a high sensitivity and paves the way for many important biomedical applications. Optical imaging techniques are becoming central to the molecular investigation of samples at the macroscopic scale, with spectrally resolved imaging used to facilitate medical diagnosis 6,7 and operations, such as in guided surgery 8,9 , because of the spectrum-dependent nature of optical contrasts. Especially, MFLI offers the advantage of high sensitivity as well as the unmixing of spectra and of fluorescence lifetime-based biomarkers. As an intrinsic characteristic of a fluorophore and its state, fluorescence lifetime can be used to investigate the molecular environment (for example, pH, ion concentration, pO 2 , temperature) 10,11 with robustness because lifetime measurements are independent of intensity, which can be significantly altered by tissue heterogeneities and depth location. Spectrally resolved Reprints and permissions information is available online at www.nature.com/reprints.

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Dynamic Optical Imaging of Metabolic and NADPH Oxidase-Derived Superoxide in Live Mouse Brain Using Fluorescence Lifetime Unmixing

Cited by 11 publications

References 0 publications

Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease

Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney disease

Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species

Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging

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