Consequences of electroshock-induced narcosis in fish muscle: from mitochondria to swim performance

International audienceAdult zebrafish Danio rerio were exposed to an electric shock of 3 V and 1A for 5 s delivered by field backpack electrofishing gear, to induce a taxis followed by a narcosis. The effect of such elec- tric shock was investigated on both the individual performances (swimming capacities and costs of transport) and at cellular and mitochondrial levels (oxygen consumption and oxidative balance). The observed survival rate was very high (96·8%) independent of swimming speed (up to 10 body length s−1). The results showed no effect of the treatment on the metabolism and cost of transport of the fish. Nor did the electroshock trigger any changes on muscular oxidative balance and bioenergetics even if red muscle fibres were more oxidative than white muscle. Phosphorylating respiration rates rose between (mean 1 s.e.) 11·16 ± 1·36 pmol O2 s−1 mg−1 and 15·63 ± 1·60 pmol O2 s−1 mg−1 for red muscle fibres whereas phosphorylating respiration rates only reached 8·73 ± 1·27 pmol O2 s−1 mg−1 in white muscle. Such an absence of detectable physiological consequences after electro-induced nar- cosis both at organismal and cellular scales indicate that this capture method has no apparent negative post-shock performance under the conditions of this study

La kinase Hippo, NDR2, contribue au phénotype migratoire/métastatique des cellules de cancer bronchique non à petites cellules

CERVOXYNational audienc

Cold-acclimation-induced non-shivering thermogenesis in birds is associated with upregulation of avian UCP but not with innate uncoupling or altered ATP efficiency

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

Warm Acclimation Increases Mitochondrial Efficiency in Fish: A Compensatory Mechanism to Reduce the Demand for Oxygen

International audienc

Doping for sex: Bad for mitochondrial performances? Case of testosterone supplemented Hyla arborea during the courtship period

© 2017 Elsevier Inc. Sexual selection has been widely explored from numerous perspectives, including behavior, ecology, and to a lesser extent, energetics. Hormones, and specifically androgens such as testosterone, are known to trigger sexual behaviors. Their effects are therefore of interest during the breeding period. Our work investigates the effect of testosterone on the relationship between cellular bioenergetics and contractile properties of two skeletal muscles involved in sexual selection in tree frogs. Calling and locomotor abilities are considered evidence of good condition in Hyla males, and thus server as proxies for male quality and attractiveness. Therefore, how these behaviors are powered efficiently remains of both physiological and behavioral interest. Most previous research, however, has focused primarily on biomechanics, contractile properties or mitochondrial enzyme activities. Some have tried to establish a relationship between those parameters but to our knowledge, there is no study examining muscle fiber bioenergetics in Hyla arborea. Using chronic testosterone supplementation and through an integrative study combining fiber bioenergetics and contractile properties, we compared sexually dimorphic trunk muscles directly linked to chronic sound production to a hindlimb muscle (i.e. gastrocnemius) that is particularly adapted for explosive movement. As expected, trunk muscle bioenergetics were more affected by testosterone than gastrocnemius muscle. Our study also underlines contrasted energetic capacities between muscles, in line with contractile properties of these two different muscle phenotypes. The discrepancy of both substrate utilization and contractile properties is consistent with the specific role of each muscle and our results are elucidating another integrative example of a muscle force-endurance trade-off

Mechanical ventilation preserves diaphragm mitochondrial function in a rat sepsis model

International audienceAbstract Background To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis. Methods A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 h after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the proinflammatory interleukin-1β (IL-1β) in diaphragms. Results CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity. Conclusion In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function

Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy

Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth