scholarly journals Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2

2019 ◽  
Vol 127 (5) ◽  
pp. 1267-1277
Author(s):  
Linjia Wang ◽  
Simin Yang ◽  
Lu Yan ◽  
Hao Wei ◽  
Jianxiong Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Treadmill Exercise ◽  
Related Factor ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypoxia Preconditioning ◽  
Nrf2 Knockout ◽  
Exercise Induced ◽  
Induced Changes

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle. NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.

scholarly journals Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle

2019 ◽  
Vol 126 (2) ◽  
pp. 477-486 ◽  
Author(s):  
Ahmed M. Wafi ◽  
Juan Hong ◽  
Tara L. Rudebush ◽  
Li Yu ◽  
Bryan Hackfort ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Exercise Performance ◽  
Antioxidant Defenses ◽  
Exercise Intolerance ◽  
Coronary Artery Ligation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Artery Ligation ◽  
Low Ejection Fraction

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg−1·day−1 for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: 1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF. NEW & NOTEWORTHY These studies suggest that impaired nuclear factor E2-related factor 2 (Nrf2) signaling is a critical mechanism underlying the enhanced oxidative stress in skeletal muscle in heart failure with low ejection fraction (HFrEF). Curcumin prevents the decline in running performance in HFrEF mice by upregulating antioxidant defenses in skeletal muscle, likely mediated by activating Nrf2 signaling. These findings suggest a novel therapeutic target for the improvement of exercise capacity and quality of life in HFrEF patients.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication

2007 ◽  
Vol 97 (03) ◽  
pp. 444-450 ◽  
Author(s):  
Rino Migliacci ◽  
Alessandra Procacci ◽  
Paola De Monte ◽  
Erminio Bonizzoni ◽  
Paolo Gresele
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Intermittent Claudication ◽  
Treadmill Exercise ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Lower Limbs ◽  
Exercise Induced ◽  
Induced Changes ◽  
Ncx 4016

SummaryIschemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day I (pre-treatment: aspirin = 3.1 ± 0.5%, nitroaspirin = 3.9 ± 0.7%, p=NS), and on day 28 (aspirin = 3.4 ± 0.7%, NCX 4016 = 3.2 ± 0.6%, p=NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = –1.15%, nitroaspirin = –1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirin-treated group (- 1.46%) while it was abolished in the NCX 4016-treated group (+ 0.79%, p= 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-l which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.

scholarly journals The B2 Receptor of Bradykinin Is Not Essential for the Post-Exercise Increase in Glucose Uptake by Insulin-Stimulated Mouse Skeletal Muscle

2011 ◽  
pp. 511-519 ◽  
Author(s):  
G. G. SCHWEITZER ◽  
C. M. CASTORENA ◽  
T. HAMADA ◽  
K. FUNAI ◽  
E. B. ARIAS ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Treadmill Exercise ◽  
Post Exercise ◽  
Skeletal Muscle Glucose Uptake ◽  
Glucose Plasma ◽  
Exercise Induced

Bradykinin can enhance skeletal muscle glucose uptake (GU), and exercise increases both bradykinin production and muscle insulin sensitivity, but bradykinin’s relationship with post-exercise insulin action is uncertain. Our primary aim was to determine if the B2 receptor of bradykinin (B2R) is essential for the post-exercise increase in GU by insulin-stimulated mouse soleus muscles. Wildtype (WT) and B2R knockout (B2RKO) mice were sedentary or performed 60 minutes of treadmill exercise. Isolated soleus muscles were incubated with [3H]-2-deoxyglucose ±insulin (60 or 100 μU/ml). GU tended to be greater for WT vs. B2RKO soleus with 60 μU/ml insulin (P=0.166) and was significantly greater for muscles with 100 μU/ml insulin (P<0.05). Both genotypes had significant exercise-induced reductions (P<0.05) in glycemia and insulinemia, and the decrements for glucose (~14 %) and insulin (~55 %) were similar between genotypes. GU tended to be greater for exercised vs. sedentary soleus with 60 μU/ml insulin (P=0.063) and was significantly greater for muscles with 100 μU/ml insulin (P<0.05). There were no significant interactions between genotype and exercise for blood glucose, plasma insulin or GU. These results indicate that the B2R is not essential for the exercise-induced decrements in blood glucose or plasma insulin or for the post-exercise increase in GU by insulin-stimulated mouse soleus muscle.

scholarly journals Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

2019 ◽  
Vol 104 (3) ◽  
pp. 407-420 ◽  
Author(s):  
Hashim Islam ◽  
Brittany A. Edgett ◽  
Jacob T. Bonafiglia ◽  
Talya Shulman ◽  
Andrew Ma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Human Skeletal Muscle ◽  
Qpcr Analysis ◽  
Exercise Induced ◽  
Induced Changes ◽  
Technical Considerations

Exercise-Induced Changes in c-Fos Protein Levels in Skeletal Muscle of Trained and Untrained Rats

2003 ◽  
Vol 24 (2) ◽  
pp. 96-100 ◽  
Author(s):  
M. G. Nikolaidis ◽  
K. T. Papazisis ◽  
A. H. Kortsaris ◽  
V. Mougios
Keyword(s):  
Skeletal Muscle ◽  
Protein Levels ◽  
Fos Protein ◽  
Exercise Induced ◽  
Induced Changes

scholarly journals OR-035 Effect of Aerobic Training on the Exercise Capacity of Apelin Knock-out Mice

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lu Yan ◽  
Tieying Li ◽  
Ying Zhang
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Oxygen Uptake ◽  
Exercise Capacity ◽  
Aerobic Training ◽  
Movement Time ◽  
Wild Type ◽  
Running Speed ◽  
Knock Out ◽  
Knock Out Mice

Objective Aerobic training is considered to be an effective way to enhance the body’s exercise capacity which is closely related to the improvement of skeletal muscle energy metabolism. And as a new myokine, apelin has been found to play a key role in regulating the energy metabolism of skeletal muscle. However, whether the loss of apelin gene affects exercise capacity and what role aerobic training play in it remains unknown. This study was designed to investigate the effect of apelin on exercise capacity during aerobic training and to provide a theoretical basis for the mechanism of aerobic exercise affecting exercise capacity. Methods Male C57BL/6J wild type mouse(n=20) and apelin knock-out mouse(n=20) were assigned by random allocation to four groups(n=10): wild type control(WC), wild type exercised(WE), apelin knock-out control(KC) and apelin knock-out exercised(KE). Exercise training consisted of treadmill running 60 minutes/day ×6 days/week for 4 weeks. The training intensity corresponded to the 70-75% maximum oxygen uptake of mice. The running speed was 15m/min with an incline of +5° in the first 2 weeks and subsequently adjusted to 20m/min according to the maximum oxygen uptake in the last 2 weeks. On the day after training, all groups were forced to perform a incremental exercise test to exhaustion. This test was started with an incline of +5°and a speed of 10 m/min for 5 min. After this initial phase, the speed was progressively increased by 3m/min every 3 min until animal exhausted. The maximum running speed, movement time and distance were recorded during the test. Results Compared with group WC, the maximum running speed, movement time and distance of group KC were significantly decreased(P<0.01). And the maximum running speed, movement time and distance of group KE were clearly higher than those of group KC(P<0.01). There is no significant difference between group WE and group WC, and between group KE and group WE. Conclusions The exercise capacity of mice was significantly decreased because of knocking out the apelin gene, and the exercise ability of apelin knock-out mice can be clearly enhanced by aerobic training.

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