Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts

Xu, He N.; Feng, Min; Nath, Kavindra; Nelson, David S.; Roman, Jeff; Zhao, Huaqing; Lin, Zhenwu; Glickson, Jerry D.; Li, Lin Z.

doi:10.1007/s11307-018-1258-z

Cited by 18 publications

(25 citation statements)

References 56 publications

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“…For FA-exposed SP-A2 mice, after imaging of the redox baseline, redox plasticity [ 47 ] was imaged by sequentially adding mitochondrial metabolic perturbation drugs to first uncouple mitochondrial oxidative phosphorylation then inhibit the mitochondrial complex I and III. Trifluoromethoxy carbonylcyanide phenylhydrazone (FCCP, 0.5 µM) was used as the uncoupler and a mixture of rotenone (1 µM) and antimycin A (1.25 µg/mL) (ROTAA) was used as the inhibitor.…”

Section: Methodsmentioning

confidence: 99%

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Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Lin

Gandhi

et al. 2020

Antioxidants

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Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner. We investigated the NAD(H) redox status of AM from SP-A2 and SP-A knockout (KO) mice in response to O3 or filtered air (control) exposure using optical redox imaging technique. We found: (i) In SP-A2 mice, the redox alteration of AM in response to O3 showed sex-dependence with AM from males being significantly more oxidized and having a higher level of mitochondrial reactive oxygen species than females; (ii) AM from KO mice were more oxidized after O3 exposure and showed no sex differences; (iii) AM from female KO mice were more oxidized than female SP-A2 mice; and (iv) Two distinct subpopulations characterized by size and redox status were observed in a mouse AM sample. In conclusions, the NAD(H) redox balance in AM responds to O3 in a sex-dependent manner and the innate immune molecule, SP-A2, contributes to this observed sex-specific redox response.

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Section: Methodsmentioning

confidence: 99%

“…Acquired images were processed with a customized routine of Matlab ® . Details of data analysis can be found in our previous reports [ 25 , 47 ]. In brief, the cell-free background signals were subtracted from each of the raw images.…”

Section: Methodsmentioning

confidence: 99%

Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Lin

Gandhi

et al. 2020

Antioxidants

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“…For Fp channel, the optical filters were 450-488 nm and 500-530 nm for excitation and emission, respectively. To confirm the collected signals reflect the redox state, redox response was obtained by first imaging the baseline of the cells, followed by sequential addition of a) carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP, 0.5 μM final concentration) and b) rotenone (ROT, 1 μM final concentration) together with antimycin A (AA, 1.25 μg/ml final concentration) and imaging accordingly, where treatment of either a) or b) was ~5 min [ 59 ]. It is known that FCCP as a mitochondrial oxidative phosphorylation uncoupler causes oxidation of NADH, resulting in a decrease in NADH.…”

Section: Methodsmentioning

confidence: 99%

“…The data acquired from optical redox imaging of C2C12 cultures were processed with Matlab ® as previously described [ 59 , 60 ]. Each image was first flattened with a surface fit function (poly33), followed by background subtraction and thresholding.…”

Section: Methodsmentioning

confidence: 99%

Rapamycin maintains NAD+/NADH redox homeostasis in muscle cells

Zhang

et al. 2020

Aging

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Rapamycin delays multiple age-related conditions and extends lifespan in organisms ranging from yeast to mice. However, the mechanisms by which rapamycin influences longevity are incompletely understood. The objective of this study was to investigate the effect of rapamycin on NAD + /NADH redox balance. We report that the NAD + /NADH ratio of C2C12 myoblasts or differentiated myotubes significantly decreases over time in culture, and that rapamycin prevents this effect. Despite lowering the NADH available to support ATP generation, rapamycin increases ATP availability, consistent with lowering energetic demand. Although rapamycin did not change the NAD + /NADH ratio or steady-state ATP concentration in the livers, kidneys, or muscles of young mice, optical redox imaging revealed that rapamycin caused a substantial decline in the NADH content and an increase in the optical redox ratio (a surrogate of NAD + /NADH redox ratio) in muscles from aged mice. Collectively, these data suggest that rapamycin favors a more oxidized NAD + /NADH ratio in aged muscle, which may influence metabolism and the activity of NAD + -dependent enzymes. This study provides new insight into the mechanisms by which rapamycin might influence the aging process to improve health and longevity among the aging population.

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“…The article entitled BOptical redox imaging of fixed unstained muscle slides reveals useful biological information^, by Xu et al, quantifies age-associated redox differences by imaging autofluorescence (across the same excitation and emission channels as used for NADH and FAD) of formalin fixed muscle slides [3]. Two other articles are by Ramanujan et al [4], and Xu et al [5], respectively. In these works, fluorescence imaging techniques were applied to investigate the treatment response of mammary tumor spheroids, and melanoma cells and xenografts, respectively.…”

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confidence: 99%

Commemorating Britton Chance

Yodh

2019

Mol Imaging Biol

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Britton Chance excelled in research, at a remarkably high level, in areas spanning biochemistry, bioengineering, biology, biophysics, chemical enginerring, electrical engineering, medicine, and physics [1]. He was a pioneer in bioenergetics, redox biology, and in vivo NMR, and was also a founding father of in vivo biomedical optics. He also led the development of radar system in the Radiation Laboratory of MIT during the World War II. At the bench, Chance measured the enzymatic kinetics, experimentally demonstrated the formation of the Michaelis-Menten enzyme-substrate complex, and he and coworkers identified the release of hydrogen peroxide by mitochondrial respiratory chain. Moreover, he was an experimental pioneer in the study and elucidation of electron-tunneling phenomena in biological systems. Throughout the time, he and his coworkers and colleagues invented many of the instruments and techniques that are widely utilized to probe biology at sub-cellular, cellular, tissue, and organ levels. Lastly, he was a leader in the translation of basic technologies to diagnostic and treatment strategies in the clinic. Among these instruments and technologies are the dualwavelength spectrometer, miniature stop-flow devices, the redox scanner, in vivo 31 P-MRS, time-resolved near-infrared spectroscopy (NIRS), photon diffusion tomography, and functional NIRS. Additionally, some of his early work included the development of a mechanical computer for solving differential equations, and the essential input for the construction of logical circuits of the ENIAC, the first general purpose electronic computer. During his life, Chance was awarded many honors including the US National Medal of Science and memberships in six Academies of Science, but perhaps his 1952 Olympic gold medal in sailing was his most legendary award. He also trained many students and researchers all over the world and thus helped build today's global research community that emphasizes research innovation, biomedical application, and clinical translation of new technologies. To celebrate his life, time, and legacy, several symposia were organized and successfully held at the University of Pennsylvania, where Chance spent nearly eight decades of his research career. These symposia were the Britton Chance

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Optical Redox Imaging of Lonidamine Treatment Response of Melanoma Cells and Xenografts

Abstract: Our results support the utility of ORI for evaluating cellular metabolism and monitoring early metabolic response to cancer drugs.

Cited by 18 publications

References 56 publications

Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Rapamycin maintains NAD+/NADH redox homeostasis in muscle cells

Commemorating Britton Chance

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