scholarly journals Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Matthew Hancock ◽  
Anne D Hafstad ◽  
Adam A Nabeebaccus ◽  
Norman Catibog ◽  
Angela Logan ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Exercise Capacity ◽  
Exercise Performance ◽  
Acute Exercise ◽  
Contractile Function ◽  
Beneficial Effects ◽  
Nadph Oxidase 4 ◽  
Endogenous Antioxidants ◽  
Exercise Induced ◽  
Nrf2 Activator

Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROS-generating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels increase during acute exercise and trigger activation of the transcription factor Nrf2, with the induction of multiple endogenous antioxidants. Cardiomyocyte-specific Nox4-deficient (csNox4KO) mice display a loss of exercise-induced Nrf2 activation, cardiac oxidative stress and reduced exercise performance. Cardiomyocyte-specific Nrf2-deficient (csNrf2KO) mice exhibit similar compromised exercise capacity, with mitochondrial and cardiac dysfunction. Supplementation with an Nrf2 activator or a mitochondria-targeted antioxidant effectively restores cardiac performance and exercise capacity in csNox4KO and csNrf2KO mice respectively. The Nox4/Nrf2 axis therefore drives a hormetic response that is required for optimal cardiac mitochondrial and contractile function during physiological exercise.

NADPH oxidase 4 mediates the protective effects of physical activity against obesity-induced vascular dysfunction

2019 ◽  
Vol 116 (10) ◽  
pp. 1767-1778 ◽  
Author(s):  
Heike Brendel ◽  
Amna Shahid ◽  
Anja Hofmann ◽  
Jennifer Mittag ◽  
Stefan R Bornstein ◽  
...  
Keyword(s):  
Physical Activity ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Intracellular Calcium ◽  
Calcium Release ◽  
Citrate Synthase ◽  
Protective Effects ◽  
Nadph Oxidase 4 ◽  
Intracellular Calcium Release ◽  
Exercise Induced

Abstract Aims Physical activity is one of the most potent strategies to prevent endothelial dysfunction. Recent evidence suggests vaso-protective properties of hydrogen peroxide (H2O2) produced by main endothelial NADPH oxidase isoform 4 (Nox4) in the vasculature. Therefore, we hypothesized that Nox4 connects physical activity with vaso-protective effects. Methods and results Analysis of the endothelial function using Mulvany Myograph showed endothelial dysfunction in wild-type (WT) as well as in C57BL/6J/ Nox4−/− (Nox4−/−) mice after 20 weeks on high-fat diet (HFD). Access to running wheels during the HFD prevented endothelial dysfunction in WT but not in Nox4−/− mice. Mechanistically, exercise led to an increased H2O2 release in the aorta of WT mice with increased phosphorylation of eNOS pathway member AKT serine/threonine kinase 1 (AKT1). Both H2O2 release and phosphorylation of AKT1 were diminished in aortas of Nox4−/− mice. Deletion of Nox4 also resulted in lower intracellular calcium release proven by reduced phenylephrine-mediated contraction, whilst potassium-induced contraction was not affected. H2O2 scavenger catalase reduced phenylephrine-induced contraction in WT mice. Supplementing H2O2 increased phenylephrine-induced contraction in Nox4−/− mice. Exercise-induced peroxisome proliferative-activated receptor gamma, coactivator 1 alpha (Ppargc1a), as key regulator of mitochondria biogenesis in WT but not Nox4−/− mice. Furthermore, exercise-induced citrate synthase activity and mitochondria mass were reduced in the absence of Nox4. Thus, Nox4−/− mice became less active and ran less compared with WT mice. Conclusions Nox4 derived H2O2 plays a key role in exercise-induced adaptations of eNOS and Ppargc1a pathway and intracellular calcium release. Hence, loss of Nox4 diminished physical activity performance and vascular protective effects of exercise.

scholarly journals Habitual physical activity mediates the acute exercise-induced modulation of anxiety-related amygdala functional connectivity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yu-Chun Chen ◽  
Chenyi Chen ◽  
Róger Marcelo Martínez ◽  
Jennifer L. Etnier ◽  
Yawei Cheng
Keyword(s):  
Physical Activity ◽  
Functional Connectivity ◽  
Acute Exercise ◽  
Neural Mechanism ◽  
Habitual Physical Activity ◽  
Treadmill Running ◽  
Beneficial Effects ◽  
Fmri Study ◽  
Exercise Induced ◽  
Amygdala Reactivity

AbstractAerobic exercise, in relation to physical activity, has been shown to have beneficial effects on anxiety. However, the underlyig neural mechanism remains elusive. Using a within-subject crossover design, this fMRI study examined how exercise (12-min treadmill running versus walking) mediated amygdala reactivity to explicit and implicit (backward masked) perception of emotional faces in young adults (N = 40). Results showed that acute exercise-induced differences of state anxiety (STAI-S) varied as a function of individual’s habitual physical activity (IPAQ). Subjects with high IPAQ levels showed significant STAI-S reduction (P < 0.05). Path analyses indicated that IPAQ explained 14.67% of the variance in acute exercise-induced STAI-S differences. Running elicited stronger amygdala reactivity to implicit happiness than fear, whereas walking did the opposite. The exercise-induced amygdala reactivity to explicit fear was associated with the IPAQ scores and STAI-S differences. Moreover, after running, the amygdala exhibited a positive functional connectivity with the orbitofrontal cortex and insula to implicit happiness, but a negative connectivity with the parahippocampus and subgenual cingulate to implicit fear. The findings suggest that habitual physical activity could mediate acute exercise-induced anxiolytic effects in regards to amygdala reactivity, and help establish exercise training as a form of anxiolytic therapy towards clinical applications.

scholarly journals Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2635
Author(s):  
Ana P. Pinto ◽  
Alisson L. da Rocha ◽  
Bruno B. Marafon ◽  
Rafael L. Rovina ◽  
Vitor R. Muñoz ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Gastrocnemius Muscle ◽  
Acute Exercise ◽  
Colchicine Treatment ◽  
Heart Tissue ◽  
Beclin 1 ◽  
Liver Protein ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Exercise Induced

Although physical exercise-induced autophagy activation has been considered a therapeutic target to enhance tissue health and extend lifespan, the effects of different exercise models on autophagy in specific metabolic tissues are not completely understood. This descriptive investigation compared the acute effects of endurance (END), exhaustive (ET), strength (ST), and concurrent (CC) physical exercise protocols on markers of autophagy, genes, and proteins in the gastrocnemius muscle, heart, and liver of mice. The animals were euthanized immediately (0 h) and six hours (6 h) after the acute exercise for the measurement of glycogen levels, mRNA expression of Prkaa1, Ppargc1a, Mtor, Ulk1, Becn1, Atg5, Map1lc3b, Sqstm1, and protein levels of Beclin 1 and ATG5. The markers of autophagy were measured by quantifying the protein levels of LC3II and Sqstm1/p62 in response to three consecutive days of intraperitoneal injections of colchicine. In summary, for gastrocnemius muscle samples, the main alterations in mRNA expressions were observed after 6 h and for the ST group, and the markers of autophagy for the CC group were increased (i.e., LC3II and Sqstm1/p62). In the heart, the Beclin 1 and ATG5 levels were downregulated for the ET group. Regarding the markers of autophagy, the Sqstm1/p62 in the heart tissue was upregulated for the END and ST groups, highlighting the beneficial effects of these exercise models. The liver protein levels of ATG5 were downregulated for the ET group. After the colchicine treatment, the liver protein levels of Sqstm1/p62 were decreased for the END and ET groups compared to the CT, ST, and CC groups. These results could be related to diabetes and obesity development or liver dysfunction improvement, demanding further investigations.

scholarly journals NADPH oxidase 4 and its role in the cardiovascular system

2019 ◽  
Vol 1 (1) ◽  
pp. H59-H66
Author(s):  
Stephen P Gray ◽  
Ajay M Shah ◽  
Ioannis Smyrnias
Keyword(s):  
Nadph Oxidase ◽  
Cardiovascular System ◽  
Contractile Function ◽  
Cellular Level ◽  
Nadph Oxidases ◽  
Nadph Oxidase 4 ◽  
Specific Effects ◽  
Different Types ◽  
Electron Reduction ◽  
Nox Family

The heart relies on complex mechanisms that provide adequate myocardial oxygen supply in order to maintain its contractile function. At the cellular level, oxygen undergoes one electron reduction to superoxide through the action of different types of oxidases (e.g. xanthine oxidases, uncoupled nitric oxide synthases, NADPH oxidases or NOX). Locally generated oxygen-derived reactive species (ROS) are involved in various signaling pathways including cardiac adaptation to different types of physiological and pathophysiological stresses (e.g. hypoxia or overload). The specific effects of ROS and their regulation by oxidases are dependent on the amount of ROS generated and their specific subcellular localization. The NOX family of NADPH oxidases is a main source of ROS in the heart. Seven distinct Nox isoforms (NOX1–NOX5 and DUOX1 and 2) have been identified, of which NOX1, 2, 4 and 5 have been characterized in the cardiovascular system. For the purposes of this review, we will focus on the effects of NADPH oxidase 4 (NOX4) in the heart.

scholarly journals Ubiquinol Supplementation Alters Exercise Induced Fatigue by Increasing Lipid Utilization in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2550 ◽  
Author(s):  
Huan-Chieh Chen ◽  
Chi-Chang Huang ◽  
Tien-Jen Lin ◽  
Mei-Chich Hsu ◽  
Yi-Ju Hsu
Keyword(s):  
Grip Strength ◽  
Exercise Performance ◽  
Acute Exercise ◽  
Serum Lactate ◽  
Reduced Form ◽  
Swimming Time ◽  
Atp Production ◽  
Beneficial Effects ◽  
Cell Energy ◽  
Forelimb Grip Strength

Ubiquinol (QH), a reduced form of coenzyme Q10, is a lipid antioxidant that is hydro-soluble and is commonly formulated in commercial supplements. Ubiquinol has been increasingly reported to exert antioxidant functions, in addition to its role in the cell energy-producing system of mitochondria and adenosine triphosphate (ATP) production. The aim of this study was to assess the potential beneficial effects of QH on anti-fatigue and ergogenic functions following physiological challenge. Forty 8-week-old male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 for each group): Group 1 (vehicle control or oil only); Group 2 (1X QH dose or 102.5 mg/kg); Group 3 (2X QH dose or 205 mg/kg); Group 4 (6X QH dose or 615 mg/kg). Anti-fatigue activity and exercise performance were studied using the forelimb grip strength experiment and exhaustive weight-loaded swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen), creatine kinase (CK), and free fatty acids (FFA) after an acute exercise challenge. The forelimb grip strength and exhaustive weight-loaded swimming time of the QH-6X group were significantly higher than those of the other groups. QH supplementation dose-dependently reduced serum lactate, ammonia, and CK levels and increased the FFA concentration after acute exercise. In addition, QH increased the liver and muscle glycogen content, an important energy source during exercise. Therefore, the results suggest that QH formulation is a safe dietary supplement for amelioration of fatigue and for promoting exercise performance.

scholarly journals Author response: Myocardial NADPH oxidase-4 regulates the physiological response to acute exercise

2018 ◽  
Author(s):  
Matthew Hancock ◽  
Anne D Hafstad ◽  
Adam A Nabeebaccus ◽  
Norman Catibog ◽  
Angela Logan ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Physiological Response ◽  
Acute Exercise ◽  
Author Response ◽  
Nadph Oxidase 4

scholarly journals Impaired exercise performance is independent of inflammation and cellular stress following genetic reduction or deletion of selenoprotein S

2020 ◽  
Vol 318 (5) ◽  
pp. R981-R996
Author(s):  
Alex Bernard Addinsall ◽  
Craig Robert Wright ◽  
Taryan L. Kotsiakos ◽  
Zoe M. Smith ◽  
Taylah R. Cook ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Knockout Mice ◽  
Exercise Performance ◽  
Contractile Function ◽  
Cellular Stress ◽  
Treadmill Running ◽  
Control Group ◽  
Wild Type ◽  
Inflammatory Stress ◽  
Selenoprotein S

Selenoprotein S (Seps1) can be protective against oxidative, endoplasmic reticulum (ER), and inflammatory stress. Seps1 global knockout mice are less active, possess compromised fast muscle ex vivo strength, and, depending on context, heightened inflammation. Oxidative, ER, and inflammatory stress modulates contractile function; hence, our aim was to investigate the effects of Seps1 gene dose on exercise performance. Seps1−/− knockout, Seps1−/+ heterozygous, and wild-type mice were randomized to 3 days of incremental, high-intensity treadmill running or a sedentary control group. On day 4, the in situ contractile function of fast tibialis anterior (TA) muscles was determined. Seps1 reduction or deletion compromised exercise capacity, decreasing distance run. TA strength was also reduced. In sedentary Seps1−/− knockout mice, TA fatigability was greater than wild-type mice, and this was ameliorated with exercise. Whereas, in Seps1+/− heterozygous mice, exercise compromised TA endurance. These impairments in exercise capacity and TA contractile function were not associated with increased inflammation or a dysregulated redox state. Seps1 is highly expressed in muscle fibers and blood vessels. Interestingly, Nos1 and Vegfa mRNA transcripts were decreased in TA muscles from Seps1−/− knockout and Seps1−/+ heterozygous mice. Impaired exercise performance with Seps1 reduction or deletion cannot be attributed to heightened cellular stress, but it may potentially be mediated, in part, by the effects of Seps1 on the microvasculature.

scholarly journals Role of exercise-induced hepatokines in metabolic disorders

2019 ◽  
Vol 317 (1) ◽  
pp. E11-E24 ◽  
Author(s):  
Gaël Ennequin ◽  
Pascal Sirvent ◽  
Martin Whitham
Keyword(s):  
Metabolic Disease ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Acute Exercise ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Future Challenges ◽  
Exercise Induced

The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have referred to the liver as an endocrine organ, since it releases specific proteins called hepatokines. Some of these hepatokines are involved in whole body metabolic homeostasis and are theorized to participate in the development of metabolic disease. In this regard, the present review describes the role of Fibroblast Growth Factor 21, Fetuin-A, Angiopoietin-like protein 4, and Follistatin in metabolic disease and their production in response to acute exercise. Also, we discuss the potential role of hepatokines in mediating the beneficial effects of regular exercise and the future challenges to the discovery of new exercise-induced hepatokines.

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