Activity of Krebs cycle enzymes in <i>mdx</i> mice

Comim, Clarissa M.; Hoepers, Andreza; Ventura, Luisa; Freiberger, Viviane; Dominguini, Diogo; Mina, Francielle; Mendonça, Bruna P.; Scaini, Giselli; Vainzof, Mariz; Streck, Emílio L.; Quevedo, Joao L De

doi:10.1002/mus.24704

Cited by 8 publications

(8 citation statements)

References 30 publications

(33 reference statements)

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“…Metabolic reprogramming in mdx and DMD muscle is complex, and likely temporally regulated in dynamic fashion. Indeed, contrary to our observation, a recent report revealed elevated activity in oxidative enzymes of the Krebs cycle in mdx diaphragm [ 44 ].…”

Section: Discussioncontrasting

confidence: 99%

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

et al. 2017

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Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in mdx diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease.

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Section: Discussioncontrasting

confidence: 99%

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

et al. 2017

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“…This deficit likely arises in part due to increased intracellular calcium [ 76 ] and muscle regeneration, resulting in an increased need for ATP production via the TCA cycle [ 77 ]. Furthermore, an increase in the activity of TCA cycle enzymes was observed in several brain and muscle tissues of the mdx mouse, suggesting that mitochondrial dysfunction and oxidative stress are part of mdx pathophysiology [ 78 ]. Additional evidence is needed to evaluate whether there is a delay in the onset of oxidative stress and muscle wasting in the slow-progressing dogs compared to fast-progressing dogs.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling of disease progression in canine model of Duchenne muscular dystrophy

et al. 2018

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Duchenne muscular dystrophy (DMD) causes progressive disability in 1 of every 5,000 boys due to the lack of functional dystrophin protein. Despite much advancement in knowledge about DMD disease presentation and progression—attributable in part to studies using mouse and canine models of the disease–current DMD treatments are not equally effective in all patients. There remains, therefore, a need for translational animal models in which novel treatment targets can be identified and evaluated. Golden Retriever muscular dystrophy (GRMD) is a phenotypically and genetically homologous animal model of DMD. As with DMD, speed of disease progression in GRMD varies substantially. However, unlike DMD, all GRMD dogs possess the same causal mutation; therefore genetic modifiers of phenotypic variation are relatively easier to identify. Furthermore, the GRMD dogs used in this study reside within the same colony, reducing the confounding effects of environment on phenotypic variation. To detect modifiers of disease progression, we developed gene expression profiles using RNA sequencing for 9 dogs: 6 GRMD dogs (3 with faster-progressing and 3 with slower-progressing disease, based on quantitative, objective biomarkers) and 3 control dogs from the same colony. All dogs were evaluated at 2 time points: early disease onset (3 months of age) and the point at which GRMD stabilizes (6 months of age) using quantitative, objective biomarkers identified as robust against the effects of relatedness/inbreeding. Across all comparisons, the most differentially expressed genes fell into 3 categories: myogenesis/muscle regeneration, metabolism, and inflammation. Our findings are largely in concordance with DMD and mouse model studies, reinforcing the utility of GRMD as a translational model. Novel findings include the strong up-regulation of chitinase 3-like 1 (CHI3L1) in faster-progressing GRMD dogs, suggesting previously unexplored mechanisms underlie progression speed in GRMD and DMD. In summary, our findings support the utility of RNA sequencing for evaluating potential biomarkers of GRMD progression speed, and are valuable for identifying new avenues of exploration in DMD research.

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“…19,41 Moreover, increased oxidative stress is characteristic of dystrophic muscle. 49,50 We found that mdx-Mss51 KO limb muscle has increased respiration capacity compared to mdx muscle. One possible explanation for the high oxidative capacity in muscle mitochondria from mdx-Mss51 KO mice is that Mss51, acting within the myostatin pathway, could act as a mediator between energy metabolism and endurance capacity in skeletal muscle.…”

Section: Discussionmentioning

confidence: 76%

Mss51 deletion increases endurance and ameliorates histopathology in the mdx mouse model of Duchenne muscular dystrophy

et al. 2021

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Abbreviations: ATP, adenosine triphosphate; high-energy molecule found in every cell; DMD, Duchenne muscular dystrophy; an inherited disorder of progressive muscle weakness; Fatty acid β-oxidation; metabolic process by which fatty acid molecules are broken down, and the beta carbon is oxidized to a carbonyl group; mdx, mouse model of Duchenne muscular dystrophy lacking dystrophin expression; mdx-Mss51 KO, mutant mouse that does not express dystrophin nor Mss51; Mss51, mitochondrial translational activator; ROS, reactive oxygen species; chemically reactive molecules that contain oxygen.

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Activity of Krebs cycle enzymes in mdx mice

Abstract: This study showed increased activity of Krebs cycle enzymes in cortex, quadriceps, and diaphragm in mdx mice.

Cited by 8 publications

References 30 publications

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

Expression profiling of disease progression in canine model of Duchenne muscular dystrophy

Mss51 deletion increases endurance and ameliorates histopathology in the mdx mouse model of Duchenne muscular dystrophy

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