“…L-NAME, ODQ and KT5823 treatment increased the expression of HSP60 and ClpP protein. The NO donor DETA-NO (80 μM) and the membrane-permeant cGMP analogue 8Br-cGMP (2.5 mM) [ 62 - 66 ] reversed the effects of L-NAME and ODQ, respectively (Figure 3 A). Figure 3 NO signalling, UPR mt , and autophagy on myogenic precursor cells.…”
BackgroundNitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOSμ on mitochondria impact on muscle function, however, has not been investigated yet.MethodsIn this study we have examined the relationship between the NO system, mitochondrial structure/activity and skeletal muscle phenotype/growth/functions using a mouse model in which nNOSμ is absent. Also, NO-induced effects and the NO pathway were dissected in myogenic precursor cells.ResultsWe show that nNOSμ deficiency in mouse skeletal muscle leads to altered mitochondrial bioenergetics and network remodelling, and increased mitochondrial unfolded protein response (UPRmt) and autophagy. The absence of nNOSμ is also accompanied by an altered mitochondrial homeostasis in myogenic precursor cells with a decrease in the number of myonuclei per fibre and impaired muscle development at early stages of perinatal growth. No alterations were observed, however, in the overall resting muscle structure, apart from a reduced specific muscle mass and cross sectional areas of the myofibres. Investigating the molecular mechanisms we found that nNOSμ deficiency was associated with an inhibition of the Akt-mammalian target of rapamycin pathway. Concomitantly, the Akt-FoxO3-mitochondrial E3 ubiquitin protein ligase 1 (Mul-1) axis was also dysregulated. In particular, inhibition of nNOS/NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent-protein kinases induced the transcriptional activity of FoxO3 and increased Mul-1 expression. nNOSμ deficiency was also accompanied by functional changes in muscle with reduced muscle force, decreased resistance to fatigue and increased degeneration/damage post-exercise.ConclusionsOur results indicate that nNOSμ/NO is required to regulate key homeostatic mechanisms in skeletal muscle, namely mitochondrial bioenergetics and network remodelling, UPRmt and autophagy. These events are likely associated with nNOSμ-dependent impairments of muscle fibre growth resulting in a deficit of muscle performance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-014-0022-6) contains supplementary material, which is available to authorized users.
“…L-NAME, ODQ and KT5823 treatment increased the expression of HSP60 and ClpP protein. The NO donor DETA-NO (80 μM) and the membrane-permeant cGMP analogue 8Br-cGMP (2.5 mM) [ 62 - 66 ] reversed the effects of L-NAME and ODQ, respectively (Figure 3 A). Figure 3 NO signalling, UPR mt , and autophagy on myogenic precursor cells.…”
BackgroundNitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOSμ on mitochondria impact on muscle function, however, has not been investigated yet.MethodsIn this study we have examined the relationship between the NO system, mitochondrial structure/activity and skeletal muscle phenotype/growth/functions using a mouse model in which nNOSμ is absent. Also, NO-induced effects and the NO pathway were dissected in myogenic precursor cells.ResultsWe show that nNOSμ deficiency in mouse skeletal muscle leads to altered mitochondrial bioenergetics and network remodelling, and increased mitochondrial unfolded protein response (UPRmt) and autophagy. The absence of nNOSμ is also accompanied by an altered mitochondrial homeostasis in myogenic precursor cells with a decrease in the number of myonuclei per fibre and impaired muscle development at early stages of perinatal growth. No alterations were observed, however, in the overall resting muscle structure, apart from a reduced specific muscle mass and cross sectional areas of the myofibres. Investigating the molecular mechanisms we found that nNOSμ deficiency was associated with an inhibition of the Akt-mammalian target of rapamycin pathway. Concomitantly, the Akt-FoxO3-mitochondrial E3 ubiquitin protein ligase 1 (Mul-1) axis was also dysregulated. In particular, inhibition of nNOS/NO/cyclic guanosine monophosphate (cGMP)/cGMP-dependent-protein kinases induced the transcriptional activity of FoxO3 and increased Mul-1 expression. nNOSμ deficiency was also accompanied by functional changes in muscle with reduced muscle force, decreased resistance to fatigue and increased degeneration/damage post-exercise.ConclusionsOur results indicate that nNOSμ/NO is required to regulate key homeostatic mechanisms in skeletal muscle, namely mitochondrial bioenergetics and network remodelling, UPRmt and autophagy. These events are likely associated with nNOSμ-dependent impairments of muscle fibre growth resulting in a deficit of muscle performance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-014-0022-6) contains supplementary material, which is available to authorized users.
“…It was indicated that in ovo injection of arginine (0.06 ml of 1% arginine solution) increased serum inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) concentration (Gao et al, 2017). Cazzato et al (2014) reported the critical role of iNOS and NO on myogenesis of chick embryo; then, in ovo injection of arginine can improve growth through activating iNOS pathway.…”
The present article was conducted to evaluate the effect of in ovo injection of arginine on hatchability, immune system and caecum microflora of broiler chickens. For this reason, 300 fertile eggs were used in a completely randomized design with three experimental treatments. The experimental groups included: 1%–0.5% l‐arginine (100 eggs), 2%–1% l‐arginine (100 eggs), 3‐ control [included both sham control (injection of distilled water; 50 eggs) and control (no injection; 50 eggs)], which were injected on d 14 of incubation. After hatching, chicks of each experimental group (0.5% l‐arginine, 1% l‐arginine, and control groups) were randomly divided into four equal groups (as replicates) and reared for 30 days. Weight and feeding of chickens were recorded. Next, blood samples of chickens were collected on day 30 to evaluate antibody titre. Also, chickens were slaughtered on 24 and 30 days of the experiment to evaluate immune system organs and caecum microflora. Based on the results, in ovo injection of l‐arginine had no significant effect on hatchability, body weight, antibody titre, spleen, bursa of Fabricius and thymus weight (p > .05). On the other hand, treatments significantly affected feed intake and feed conversion ratio (p < .05). As a novel finding, in ovo injection of l‐arginine increased caecal Lactobacillus (p < .01), while decreasing Coliform and Escherichia Coli bacteria (p < .01). However, treatments did not influence caecal Enterococcus (p > .05). The overall results indicated that in ovo injection of 0.5% l‐arginine had a better improving effect on caecal microflora and then considered as a recommended level of the present experiment.
“…Animal and in vivo human studies have linked NO signaling to cell proliferation and differentiation, angiogenesis, myogenesis, cardiogenesis, neurogenesis, lymphangiogenesis, and bone formation, among other critical developmental events. 34–40 NO is also central to fetal and neonatal hemodynamics during the perinatal transition period. NO appears to be involved in maintenance of a relatively high cardiac output state of the fetus.…”
Background
Nitric oxide (NO) and its derivatives play important roles in the cardiopulmonary transition upon birth and in other oxygen-sensitive developmental milestones. One mechanism for the coupling of oxygen sensing and signaling by NO species is via the formation of an S-nitrosothiol (SNO) moiety on hemoglobin (Hb, forming SNO-Hb) and its release from the red blood cell in hypoxia. Although SNO-Hb formed on adult-type Hb (HbA, forming SNO-HbA) has been documented in physiological and pathophysiological human states, the fetal variant, SNO-HbF, has thus far not been isolated or characterized in human blood.
Methods and Results
We developed a technique capable of separating Hbs A and F under conditions that preserve SNO. We then measured SNO-HbF in the blood of healthy and premature or otherwise ill neonates using the gold standard for SNO measurement, mercury-coupled photolysis-chemiluminescence. SNO-HbF levels were in the range of those previously reported for HbA in adults. We found that SNO-HbF was more abundant at earlier gestational age (<30 weeks), even when accounting for the absolute HbF level.
Conclusions
The ability to monitor SNO-HbF could provide new insights into fetal development and the perinatal transition, and has potential as a biomarker relevant to the management of neonatal diseases.
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