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| 2. |
- Ferreira, Duarte M. S., et al.
(author)
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LIM and cysteine-rich domains 1 (LMCD1) regulates skeletal muscle hypertrophy, calcium handling, and force
- 2019
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In: Skeletal Muscle. - : BioMed Central. - 2044-5040. ; 9:1
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Journal article (peer-reviewed)abstract
- Background: Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia.Methods: We analyzed gene expression data from muscle of mice or human patients with diverse muscle pathologies and identified LMCD1 as a gene strongly associated with skeletal muscle function. We transiently expressed or silenced LMCD1 in mouse gastrocnemius muscle or in mouse primary muscle cells and determined muscle/cell size, targeted gene expression, kinase activity with kinase arrays, protein immunoblotting, and protein synthesis levels. To evaluate force, calcium handling, and fatigue, we transduced the flexor digitorum brevis muscle with a LMCD1-expressing adenovirus and measured specific force and sarcoplasmic reticulum Ca2+ release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling.Results: Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease.Conclusions: Our gain- and loss-of-function studies show that LMCD1 controls protein synthesis, muscle fiber size, specific force, Ca2+ handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.
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| 5. |
- Chaillou, Thomas, 1985-, et al.
(author)
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Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy
- 2017
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In: Physiological Reports. - : American Physiological Society. - 2051-817X. ; 5:11
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Journal article (peer-reviewed)abstract
- Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy per se on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24h and 72h after a single injection of docetaxel (acute treatment), and 7days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24h after a single injection of docetaxel (-17%, P=0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.
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| 6. |
- Chaillou, Thomas, 1985-, et al.
(author)
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Identification of a conserved set of upregulated genes in mouse skeletal muscle hypertrophy and regrowth
- 2015
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In: Journal of applied physiology. - Bethesda, USA : American Physiological Society. - 8750-7587 .- 1522-1601. ; 118, s. 86-97
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Journal article (peer-reviewed)abstract
- The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading.
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| 7. |
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| 8. |
- Chaillou, Thomas, 1985-, et al.
(author)
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NDUFA4L2 : Connecting metabolic signals and mitochondrial function in cardiac and skeletal muscle
- 2016
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In: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 100:Suppl., s. S186-S186
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Journal article (peer-reviewed)abstract
- The nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) was recently identified. NDUFAe4L2 is shown to be induced by hypoxia via HIF1α and is thought to inhibit production of mitochondrial reactive oxygen species in fibroblasts exposed to hypoxia. Here the aim was to characterize the role of NDUFA4L2 in the mitochondria-rich tissues skeletal and cardiac muscle. We show hypoxia induced NDUFA4L2 expression in isolated muscle fibers and in cardiomyocytes with full activation after ~3-6 h in hypoxia. The half-maximal O2 level for NDUFA4L2 expression (~4.6 % of ambient O2) suggests sensitivity to changes in O2 tension that occur under physiological conditions (e.g. exercise, moderate ischemia). We identified that the NDUFA4L2 gene promoter has binding sites for transcription factors other than HIF-1α; repetitive sites for PPARα,γ and one for Nrf2. NDUFA4L2 overexpression resulted in functional effects on skeletal and cardiac muscle; e.g. it alters cellular Ca2+ signaling and the expression of Ca2+ handling genes. Further, NDUFA4L2 overexpression reduces muscle mass (~20%), leading to a decreased force production in skeletal muscle. The NDUFA4L2-induced loss of muscle mass was associated with increases in mRNA levels of e.g. MurF1, Mul1, caspase-3 and Bax. Additionally, femoral artery ligation (FAL) induced NDUFA4L2 expression, which correlates with the decreased force production eight days post-FAL in skeletal muscle. Moreover, NDUFA4L2 upregulates antioxidant gene expression and silencing NDUFA4L2 makes cardiac cells less tolerant to hypoxia/re-oxygenation. Our results suggest that NDUFA4L2 expression affects vital functions in muscle cells and at least part of this effect is mediated by a link between NDUFA4L2 and nuclear gene expression. Thus, NDUFA4L2 might act as an integrator of the nutritional, environmental and functional status in muscle cells.
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| 9. |
- Chaillou, Thomas, 1985-, et al.
(author)
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Regulation of myogenesis and skeletal muscle regeneration : effects of oxygen levels on satellite cell activity
- 2016
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In: The FASEB Journal. - Bethesda, USA : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 30:12, s. 3929-3941
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Research review (peer-reviewed)abstract
- Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.
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| 13. |
- Cheng, Arthur J., et al.
(author)
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Intact single muscle fibres from SOD1(G93A) amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training-like adaptations
- 2019
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In: Journal of Physiology. - : Cambridge University Press. - 0022-3751 .- 1469-7793. ; 597:12, s. 3133-3146
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Journal article (peer-reviewed)abstract
- Key points:How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated.Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force.On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance.These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype.Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.
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| 14. |
- Cheng, Arthur J., et al.
(author)
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Post-exercise recovery of contractile function and endurance in humans and mice is accelerated by heating and slowed by cooling skeletal muscle
- 2017
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In: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 595:24, s. 7413-7426
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Journal article (peer-reviewed)abstract
- Key points: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of ˜ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate.Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca2+] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.
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| 15. |
- Faiss, R, et al.
(author)
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Elevated Temperature Accelerates Recovery of Mouse and Human Skeletal Muscle Following Fatigue
- 2015
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In: Abstract Book for the 20th Annual <em>ECSS</em> Congress.
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Conference paper (peer-reviewed)abstract
- IntroductionThis study was designed to determine whether elevated muscle temperature allows muscles to recover their force or power more rapidly following fatigueMethodsIntact single fibers from mouse flexor digitorum brevis muscle were fatigued at 31˚C (70-Hz 350-ms tetani once every 10s until initial force decreased to 30%). During a subsequent 2-hr recovery period, the fibers were perfused in Tyrode solution at either 31°C (physiological temperature) or 36°C and isometric force and cytoplasmic free [Ca2+] ([Ca2+]i) were measured during 30-Hz tetani evoked periodically. In addition, seven human subjects performed fatiguing arm exercise consisting of 3 x 5min maximal effort arm cycling at 100 rpm followed by 4 x 15 min at an intensity of 50% of VO2peak. Then followed 2hr of recovery during which both arms were either heated or not heated at 5˚C above physiological temperatures using arm cuffs continuously perfused with temperature-regulated water; the order of heating vs. not heating was randomized between two visits. Intramuscular temperature was recorded with probes inserted 1.5 cm into the lateral head of the triceps brachii muscle. During the recovery period, subjects consumed 1.0 g/hr/kg body weight carbohydrates to support glycogen repletion. After recovery, the subjects repeated the 3 x 5 min time trials to evaluate the effect of the recovery intervention.ResultsRecovery from fatigue in mouse single fibers was dependent on muscle glycogen restoration since fibers perfused with glucose-free Tyrode did not recover contractile force (P<0.05). After 30 min of recovery, the tetanic [Ca2+]i was 107±10% and 92 ± 8% and the corresponding forces were 69±15% vs.49±14% of the initial values for the heated and non-heated muscles, respectively. In seven human subjects, 2h of muscle heating also appeared to improve muscle recovery, leading to higher mean power output in the post-recovery arm cycling time trial than without muscle heating.DiscussionElevating muscle temperature by 5°C above physiological temperature accelerates recovery in mouse muscle in-vitro and in human skeletal muscle in-vivo and this appears to depend on faster muscle glycogen resynthesis following fatigue.
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| 16. |
- Kirby, T.J., et al.
(author)
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Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis
- 2015
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In: Journal of applied physiology. - Bethesda, USA : American Physiological Society. - 8750-7587 .- 1522-1601. ; 119:4, s. 321-327
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Journal article (peer-reviewed)abstract
- The ability of skeletal muscle to hypertrophy in response to a growth stimulus is known to be compromised in older individuals. We hypothesized that a change in the expression of protein-encoding genes in response to a hypertrophic stimulus contributes to the blunted hypertrophy observed with aging. To test this hypothesis, we determined gene expression by microarray analysis of plantaris muscle from 5- and 25-mo-old mice subjected to 1, 3, 5, 7, 10, and 14 days of synergist ablation to induce hypertrophy. Overall, 1,607 genes were identified as being differentially expressed across the time course between young and old groups; however, the difference in gene expression was modest, with cluster analysis showing a similar pattern of expression between the two groups. Despite ribosome protein gene expression being higher in the aged group, ribosome biogenesis was significantly blunted in the skeletal muscle of aged mice compared with mice young in response to the hypertrophic stimulus (50% vs. 2.5-fold, respectively). The failure to upregulate pre-47S ribosomal RNA (rRNA) expression in muscle undergoing hypertrophy of old mice indicated that rDNA transcription by RNA polymerase I was impaired. Contrary to our hypothesis, the findings of the study suggest that impaired ribosome biogenesis was a primary factor underlying the blunted hypertrophic response observed in skeletal muscle of old mice rather than dramatic differences in the expression of protein-encoding genes. The diminished increase in total RNA, pre-47S rRNA, and 28S rRNA expression in aged muscle suggest that the primary dysfunction in ribosome biogenesis occurs at the level of rRNA transcription and processing.
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| 17. |
- Kirby, T.J., et al.
(author)
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The role of microRNAs in skeletal muscle health and disease
- 2015
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In: Frontiers in Bioscience. - Irvine, USA : Frontiers in Bioscience. - 1093-9946 .- 1093-4715. ; 20, s. 37-77
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Journal article (peer-reviewed)abstract
- Over the last decade non-coding RNAs have emerged as importance regulators of gene expression. In particular, microRNAs are a class of small RNAs of ∼ 22 nucleotides that repress gene expression through a post-transcriptional mechanism. MicroRNAs have been shown to be involved in a broader range of biological processes, both physiological and pathological, including myogenesis, adaptation to exercise and various myopathies. The purpose of this review is to provide a comprehensive summary of what is currently known about the role of microRNAs in skeletal muscle health and disease.
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| 18. |
- Liu, Zhengye, et al.
(author)
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Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force
- 2021
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In: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:12
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Journal article (peer-reviewed)abstract
- The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD(+) levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ec-topically expressed NDUFA4L2 caused a similar to 20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD(+), which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.
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| 19. |
- Mader, Theresa, et al.
(author)
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Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer
- 2022
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In: Journal of Cachexia, Sarcopenia and Muscle. - : John Wiley & Sons. - 2190-5991 .- 2190-6009. ; 13:2, s. 1151-1163
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are largely unknown.METHODS: Eight-week-old breast cancer (MMTV-PyMT, PyMT) and control (WT) mice had access to active or inactive in-cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC-1α, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and β-hydroxyacyl-CoA-dehydrogenase (βHAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (MAPK) signalling.RESULTS: PyMT mice endured shorter time and distance during the treadmill test (~30%, P < 0.05) and ex vivo force measurements revealed ~25% weaker slow-twitch soleus muscle (P < 0.001). This was independent of cancer-induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF-α and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer-induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced β-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFα-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1α expression, and CS and β-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease.CONCLUSIONS: Four-week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.
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| 20. |
- Wilson, Stephanie J., et al.
(author)
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Global subterranean estuaries modify groundwater nutrient loading to the ocean
- 2024
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In: Limnology And Oceanography Letters. - 2378-2242.
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Journal article (peer-reviewed)abstract
- Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater-derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.
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