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ABSTRACT: Although several lines of evidence link muscle-derived oxidants and inflammation to skeletal muscle wasting via regulation of apoptosis and proteolysis, little information is currently available on muscle repair. The present work was designed to study oxidative stress response, inflammatory cytokines, apoptotic, or proteolytic pathways during the early (1 and 5 days) and later (14 days) stages of the regrowth process subsequent to 14 days of hindlimb unloading. During the early stages of reloading, muscle mass recovery (day 5) was facilitated by transcriptional downregulation (day 1) of pathways involved in muscle proteolysis [mu-calpain, atrogin-1/muscle atrophy F-box (MAFbx), and muscle RING finger-1/(MuRF1) mRNA] and upregulation of an autophagy-related protein Beclin-1 (day 5). At the same time, oxidative stress (glutathione vs. glutathione disulfide ratio, superoxide dismutase, catalase activities) remained still enhanced, whereas the increased uncoupling protein 3 gene expression recovered. Increased caspase-9 (mitochondrial-driven apoptosis) and decreased caspase-12 (sarcoplasmic reticulum-mediated apoptosis) activation was also normalized at early stages (day 5). Conversely, the receptor-mediated apoptotic pathway initiated by ligand-induced (tumor necrosis factor-alpha, TNF-alpha) binding and promoting the activation of caspase-8 remained elevated until 14 days. Our data suggest that at early stages, muscle repair is mediated via the modulation of mitochondrial-driven apoptosis and muscle proteolysis. Despite full muscle mass recovery, oxidative stress and TNF-alpha-mediated apoptotic pathway are still activated till later stages of muscle remodeling.
AJP Cell Physiology 08/2010; 299(2):C307-15. · 3.54 Impact Factor
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ABSTRACT: Despite their lack of brown adipose tissue, some bird species develop regulatory non-shivering thermogenesis (NST) of skeletal muscle origin in response to cold acclimation. Mechanisms involved in avian NST are still unclear but may involve reduced energetic coupling in skeletal muscle mitochondria through the expression of an avian homologue of mammalian uncoupling proteins. The aim of this work was to investigate whether the expression of avian uncoupling protein (avUCP) would correlate with the capacity for cold-induced muscle NST. Various levels of cold acclimation were obtained by rearing 1-week-old ducklings (Cairina moschata) for 4 weeks at three different ambient temperatures (25 degrees C, 11 degrees C or 4 degrees C). Muscle NST was measured by simultaneous recordings of metabolic rate and electromyographic activity (gastrocnemius muscle) at ambient temperatures (T(a)) ranging from 27 degrees C to -5 degrees C. The expression of avUCP gene and mitochondrial bioenergetics were also determined in gastrocnemius muscle. Results showed that muscle NST capacity depends on the T(a) at which ducklings were acclimated, i.e. the lower the rearing temperature, the higher the capacity for NST. This increased metabolic heat production occurred in parallel with an upregulation of avUCP, which was not associated with a change in mitochondrial membrane conductance. The intensity of mitochondrial oxidative phosphorylation also increased in proportion with the harshness of cold, while the efficiency of ATP generation was equally effective in all three acclimation temperatures. In the absence of mitochondrial uncoupling, these data indicate a clear link between avUCP expression and the capacity of ducklings to adjust their muscular aerobic activity to cold exposure.
Journal of Experimental Biology 07/2010; 213(Pt 14):2476-82. · 3.00 Impact Factor
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ABSTRACT: Here we report the partial nucleotide sequence of a reptilian uncoupling protein (repUCP) gene from the European common lizard (Lacerta vivipara). Overlapping sequence analysis reveals that the protein shows 55%, 72% and 77% sequence homology with rat UCP1, UCP2 and UCP3, respectively, and 73% with bird and fish UCPs. RepUCP gene expression was ubiquitously detected in 4 degrees C cold-acclimated lizard tissues and upregulated in muscle tissues by a 20 h exposure to sub-zero temperatures in a supercooling state or after thawing. In parallel, we show an increase in the co-activators, peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and peroxisome proliferator-activated receptors (PPAR), mRNA expression, suggesting that the mechanisms regulating UCP expression may be conserved between mammals (endotherms) and reptiles (ectotherms). Furthermore, mitochondria extracted from lizard skeletal muscle showed a guanosine diphosphate (GDP)-sensitive non phosphorylating respiration. This last result indicates an inhibition of extra proton leakage mediated by an uncoupling protein, providing arguments that repUCP is functional in lizard tissues. This result is associated with a remarkable GDP-dependent increase in mitochondrial endogenous H(2)O(2) production. All together, these data support a physiological role of the repUCP in superoxide limitation by lizard mitochondria in situations of stressful oxidative reperfusion following a re-warming period in winter.
Journal of Experimental Biology 06/2008; 211(Pt 9):1456-62. · 3.00 Impact Factor
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Caroline Romestaing,
Marie-Astrid Piquet, Dominique Letexier,
Benjamin Rey,
Arnaud Mourier,
Stéphane Servais,
Maud Belouze,
Vincent Rouleau,
Marianne Dautresme,
Isabelle Ollivier,
Roland Favier,
Michel Rigoulet,
Claude Duchamp,
Brigitte Sibille
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) has become common liver disease in Western countries. There is accumulating evidence that mitochondria play a key role in NAFLD. Nevertheless, the mitochondrial consequences of steatohepatitis are still unknown. The bioenergetic changes induced in a methionine- and choline-deficient diet (MCDD) model of steatohepatitis were studied in rats. Liver mitochondria from MCDD rats exhibited a higher rate of oxidative phosphorylation with various substrates, a rise in cytochrome oxidase (COX) activity, and an increased content in cytochrome aa3. This higher oxidative activity was associated with a low efficiency of the oxidative phosphorylation (ATP/O, i.e., number of ATP synthesized/natom O consumed). Addition of a low concentration of cyanide, a specific COX inhibitor, restored the efficiency of mitochondria from MCDD rats back to the control level. Furthermore, the relation between respiratory rate and protonmotive force (in the nonphosphorylating state) was shifted to the left in mitochondria from MCDD rats, with or without cyanide. These results indicated that, in MCDD rats, mitochondrial ATP synthesis efficiency was decreased in relation to both proton pump slipping at the COX level and increased proton leak although the relative contribution of each phenomenon could not be discriminated. MCDD mitochondria also showed a low reactive oxygen species production and a high lipid oxidation potential. We conclude that, in MCDD-fed rats, liver mitochondria exhibit an energy wastage that may contribute to limit steatosis and oxidative stress in this model of steatohepatitis.
AJP Endocrinology and Metabolism 02/2008; 294(1):E110-9. · 4.75 Impact Factor
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ABSTRACT: Exposure to reduced activity induces skeletal muscle atrophy. Oxidative stress might contribute to muscle wasting via proteolysis activation. This study aimed to test two hypotheses in rats. First, supplementation of the antioxidant vitamin E, prior and during the phase of unloading, would partly counteract unloading-induced soleus muscle atrophy. Secondly, vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains, caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx). Soleus muscle atrophy (-49%) induced by 14 days of hindlimb unloading was reduced to only 32% under vitamin E. Vitamin E partly prevented the decrease in type I and IIa fiber size. Supplementation increased HSP72 content and suppressed the rise in muscle level of thiobarbituric acid-reactive substance caused by unloading but failed to modify the lower ratio of reduced vs oxidized glutathione, the higher uncoupling proteins mRNA, and the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) observed after unloading. Vitamin E treatment abolished the large upregulation of caspases-9 and -12 and MuRF1 transcripts in unloaded muscle and greatly decreased the upregulation of mu-calpain, caspase-3, and MAFbx mRNA. In conclusion, the protective effect of vitamin E might be due to modulation of muscle proteolysis-related genes rather than to its antioxidant function.
Free Radical Biology and Medicine 04/2007; 42(5):627-35. · 5.42 Impact Factor
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Blandine Garait,
Karine Couturier,
Stéphane Servais, Dominique Letexier,
David Perrin,
Cécile Batandier,
Jean-Louis Rouanet,
Brigitte Sibille,
Benjamin Rey,
Xavier Leverve,
Roland Favier
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ABSTRACT: Food restriction is the most effective modulator of oxidative stress and it is believed that a reduction in caloric intake per se is responsible for the reduced generation of reactive oxygen species (ROS) by mitochondria. Hydrogen peroxide (H(2)O(2)) generation and oxygen consumption (O(2)) by skeletal muscle mitochondria were determined in a peculiar strain of rats (Lou/C) characterized by a self-low-caloric intake and a dietary preference for fat. These rats were fed either with a standard high-carbohydrate (HC) or a high-fat (HF) diet and the results were compared to those measured in Wistar rats fed a HC diet. H(2)O(2) production was significantly reduced in Lou/C rats fed a HC diet; this effect was not due to a lower O(2) consumption but rather to a decrease in rotenone-sensitive NADH-ubiquinone oxidoreductase activity and increased expression of uncoupling proteins 2 and 3. The reduced H(2)O(2) generation displayed by Lou/C rats was accompanied by a significant inhibition of permeability transition pore (PTP) opening. H(2)O(2) production was restored and PTP inhibition was relieved when Lou/C rats were allowed to eat a HF diet, suggesting that the reduced oxidative stress provided by low caloric intake is lost when fat proportion in the diet is increased.
Free Radical Biology and Medicine 12/2005; 39(9):1249-61. · 5.42 Impact Factor
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Blandine Garait,
Karine Couturier,
Stéphane Servais, Dominique Letexier,
David Perrin,
Cécile Batandier,
Jean-Louis Rouanet,
Brigitte Sibille,
Benjamin Rey,
Xavier Leverve,
Roland Favier
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ABSTRACT: Food restriction is the most effective modulator of oxidative stress and it is believed that a reduction in caloric intake per se is responsible for the reduced generation of reactive oxygen species (ROS) by mitochondria. Hydrogen peroxide (H2O2) generation and oxygen consumption (O2) by skeletal muscle mitochondria were determined in a peculiar strain of rats (Lou/C) characterized by a self-low-caloric intake and a dietary preference for fat. These rats were fed either with a standard high-carbohydrate (HC) or a high-fat (HF) diet and the results were compared to those measured in Wistar rats fed a HC diet. H2O2 production was significantly reduced in Lou/C rats fed a HC diet; this effect was not due to a lower O2 consumption but rather to a decrease in rotenone-sensitive NADH-ubiquinone oxidoreductase activity and increased expression of uncoupling proteins 2 and 3. The reduced H2O2 generation displayed by Lou/C rats was accompanied by a significant inhibition of permeability transition pore (PTP) opening. H2O2 production was restored and PTP inhibition was relieved when Lou/C rats were allowed to eat a HF diet, suggesting that the reduced oxidative stress provided by low caloric intake is lost when fat proportion in the diet is increased.
Free Radical Biology and Medicine.
