A New Strategy to Preserve and Assess Oxygen Consumption in Murine Tissues

Kluza, Jérôme; Peugnet, Victoriane; Daunou, Blanche; Laine, William; Kervoaze, Gwenola; Rémy, Gaëlle; Loyens, Anne; Maboudou, Patrice; Fovez, Quentin; Grangette, Corinne; Wolowczuk, Isabelle; Gosset, Philippe; Garçon, Guillaume; Marchetti, Philippe; Pinet, Florence; Pichavant, Muriel; Dubois‐Deruy, Emilie

doi:10.3390/ijms23010109

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…We quantitated mitochondrial respiration in the left ventricle myocardium of sham and MI hearts at endpoint, performing parallel respirometry analyses of basal oxygen consumption rate (OCR) in freshly collected myocardial slices [ 33 ] and of RCR in isolated mitochondria. Treatment increased tissue OCR and mitochondrial RCR in sham and MI hearts, rescuing the levels in MI hearts to levels like in control sham hearts ( Figure 2 E).…”

Section: Resultsmentioning

confidence: 99%

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

Wintzinger

Panta

Miz

et al. 2022

Molecular Metabolism

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Section: Resultsmentioning

confidence: 99%

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

Wintzinger

Panta

Miz

et al. 2022

Molecular Metabolism

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“…Basal tissue OCR values were obtained from basal rates of oxygen consumption of myocardial tissue slices at the Seahorse XF96 Extracellular Flux Analyzer platform (Agilent, Santa Clara, CA) following reported conditions [33] and as we previously detailed for tissue OCR analyses in dystrophic mice [54]. For cardiomyocytes, respirometry was performed on freshly isolated cells.…”

Section: Methodsmentioning

confidence: 99%

“…We quantitated mitochondrial respiration in the left ventricle myocardium of sham and MI hearts at endpoint, performing parallel respirometry analyses of basal oxygen consumption rate (OCR) in freshly collected myocardial slices [33] and of RCR in isolated mitochondria. Treatment increased tissue OCR and mitochondrial RCR in sham and MI hearts, rescuing the levels in MI hearts to levels like in control sham hearts (Fig.…”

Section: D)mentioning

confidence: 99%

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

Wintzinger

Panta

Miz

et al. 2021

Preprint

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Bioenergetic capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates cardiac bioenergetics through the primary receptor of these drugs, the glucocorticoid receptor (GR). While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism and heart function in dystrophic mice. However, the effects of glucocorticoid intermittence on heart failure beyond muscular dystrophy remain unknown. Here we investigated the extent to which circadian time of dosing regulates the cardiac-autonomous effects of the glucocorticoid prednisone in conditions of single pulse or chronic intermittent dosing. In WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted GR ablation, and depended on an intact activating clock complex, as shown by hearts from BMAL1-KO mice. Conjugating time-of-dosing with chronic intermittence, we found that once-weekly light-phase prednisone improved metabolism and function in heart after myocardial injury. Our study identifies cardiac-autonomous mechanisms through which circadian time and chronic intermittence reconvert glucocorticoid drugs to bioenergetic boosters for the heart.

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“…Real-time extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured using the Seahorse XFe24 flux analyzer (Seahorse Bioscience, Agilent) as described previously [61]. Briefly, BMDMs were seeded at a density of 1.6×10 6 cells/ml the day before the measurement and incubated at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

IRG1 controls host responses to restrict Mycobacterium tuberculosis infection

Hoffmann

Machelart

Belhaouane

et al. 2019

Preprint

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Mycobacterium tuberculosis (Mtb), the pathogen causing human tuberculosis, has evolved multiple strategies to successfully prevent clearance by immune cells and to establish dissemination and long-term survival in the host. The modulation of host immunity to maximize pathogen elimination while minimizing inflammation-mediated tissue damage may provide another tool to fight drug-resistant Mtb strains.Metabolic reprogramming of immune cell populations can dramatically influence the outcome of immune responses and modulate antimicrobial properties of infected host cells, nicely demonstrating that metabolites are tightly linked to immune cell effector functions. One important endogenous metabolite of the Krebs cycle is itaconate, which has potent bactericidal activity by inhibiting isocitrate lyase and the glyoxylate shunt within prokaryotes including mycobacteria. Recent findings show that itaconate and the catalytic enzyme responsible for its generation in mammalian cells, i.e. IRG1 (immune-responsive gene 1), also modify inflammatory signaling of infected cells enhancing host defense pathways.Here, we demonstrate that IRG1 is recruited to Mtb-containing phagosomes and that it influences the host response controlling Mtb infection. While IRG1 deficiency does not affect uptake of Mtb by macrophages and dendritic cells (DCs) in vitro, it increases the intracellular replication of Mtb. Concomitantly, in comparison to wild type cells, IRG1-deficient macrophages and DCs have increased levels of lipid droplets, a correlate of inflammation. These intracellular organelles store triacylglycerol and phospholipids that are hijacked by Mtb as reservoir of host nutrients. Exposure of IRG1-deficient mice to M. bovis BCG via the intranasal route induced neither lethality nor severe lung immunopathology, while IRG1-deficient mice were highly susceptible to Mtb infection resulting in animal death three weeks post-infection linked to exacerbated inflammation and high mycobacterial burden. The lungs of infected IRG1-deficient mice displayed large areas of necrotizing granulomatous inflammation and neutrophil infiltration, accompanied by reduced levels of B and T lymphocytes and increased levels of alveolar and interstitial macrophage populations, compared to their wild type counterparts. Therefore, our findings demonstrate that IRG1 is a major player in controlling the acute phase of Mtb infection with a specific effect on pathogenic mycobacteria.

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A New Strategy to Preserve and Assess Oxygen Consumption in Murine Tissues

Cited by 8 publications

References 27 publications

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids

IRG1 controls host responses to restrict Mycobacterium tuberculosis infection

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