Hypoxia-induced reactive oxygen species formation in skeletal muscle

2007 ◽  
Vol 102 (6) ◽  
pp. 2379-2388 ◽  
Author(s):  
Thomas L. Clanton
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Cell Function ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Hypoxic Exposure ◽  
Ros Production ◽  
Oxygen Species

The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supportive of this idea. Skeletal muscle appears to behave much like heart in that in the early stages of hypoxia there is a transient elevation in ROS, whereas in chronic exposure to very severe hypoxia there is evidence of ongoing oxidative stress. Important remaining questions that are addressed in this review include the following. Are there levels of Po2 in skeletal muscle, typical of physiological or mildly pathophysiological conditions, that are low enough to induce significant ROS production? Does the ROS associated with muscle contractile activity reflect imbalances in oxygen uptake and demand that drive the cell to a more reduced state? What are the possible molecular mechanisms by which ROS may be elevated in hypoxic skeletal muscle? Is the production of ROS in hypoxia of physiological significance, both with respect to cell signaling pathways promoting cell function and with respect to damaging effects of long-term exposure? Discussion of these and other topics leads to general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli. However, in chronic and extreme hypoxic exposure, muscles may fail to maintain a normal redox homeostasis, resulting in cell injury or dysfunction.

scholarly journals β-Aminobutyric Acid Primes an NADPH Oxidase–Dependent Reactive Oxygen Species Production During Grapevine-Triggered Immunity

2010 ◽  
Vol 23 (8) ◽  
pp. 1012-1021 ◽  
Author(s):  
Carole Dubreuil-Maurizi ◽  
Sophie Trouvelot ◽  
Patrick Frettinger ◽  
Alain Pugin ◽  
David Wendehenne ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Aminobutyric Acid ◽  
Ros Production ◽  
Oxygen Species ◽  
Defense Gene Expression ◽  
Diphenylene Iodonium ◽  
Signaling Events

The molecular mechanisms underlying the process of priming are poorly understood. In the present study, we investigated the early signaling events triggered by β-aminobutyric acid (BABA), a well-known priming-mediated plant resistance inducer. Our results indicate that, in contrast to oligogalacturonides (OG), BABA does not elicit typical defense-related early signaling events nor defense-gene expression in grapevine. However, in OG-elicited cells pretreated with BABA, production of reactive oxygen species (ROS) and expression of the respiratory-burst oxidase homolog RbohD gene were primed. In response to the causal agent of downy mildew Plasmopara viticola, a stronger ROS production was specifically observed in BABA-treated leaves. This process was correlated with an increased resistance. The NADPH oxidase inhibitor diphenylene iodonium (DPI) abolished this primed ROS production and reduced the BABA-induced resistance (BABA-IR). These results suggest that priming of an NADPH oxidase–dependent ROS production contributes to BABA-IR in the Vitis-Plasmopara pathosystem.

scholarly journals Reactive oxygen species formation during tetanic contractions in single isolated Xenopus myofibers

2011 ◽  
Vol 111 (3) ◽  
pp. 898-904 ◽  
Author(s):  
Li Zuo ◽  
Leonardo Nogueira ◽  
Michael C. Hogan
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Real Time ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Fatigue Development ◽  
Species Formation ◽  
Significant Difference

Contracting skeletal muscle produces reactive oxygen species (ROS) that have been shown to affect muscle function and adaptation. However, real-time measurement of ROS in contracting myofibers has proven to be difficult. We used amphibian ( Xenopus laevis) muscle to test the hypothesis that ROS are formed during contractile activity in isolated single skeletal muscle fibers and that this contraction-induced ROS formation affects fatigue development. Single myofibers were loaded with 5 μM dihydrofluorescein-DA (Hfluor-DA), a fluorescent probe that reacts with ROS and results in the formation of fluorescein (Fluor) to precisely monitor ROS generation within single myofibers in real time using confocal miscroscopy. Three identical periods of maximal tetanic contractions (1 contraction/3 s for 2 min, separated by 60 min of rest) were conducted by each myofiber ( n = 6) at 20°C. Ebselen (an antioxidant) was present in the perfusate (10 μM) during the second contractile period. Force was reduced by ∼30% during each of the three contraction periods, with no significant difference in fatigue development among the three periods. The Fluor signal, indicative of ROS generation, increased significantly above baseline in both the first (42 ± 14%) and third periods (39 ± 10%), with no significant difference in the increase in fluorescence between the first and third periods. There was no increase of Fluor in the presence of ebselen during the second contractile period. These results demonstrated that, in isolated intact Xenopus myofibers, 1) ROS can be measured in real time during tetanic contractions, 2) contractile activity induced a significant increase above resting levels of ROS production, and 3) ebselen treatment reduced ROS generation to baseline levels but had no effect on myofiber contractility and fatigue development.

scholarly journals A Study on Myogenesis by Regulation of Reactive Oxygen Species and Cytotoxic Activity by Selenium Nanoparticles

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1727
Author(s):  
Sang-Cheol Lee ◽  
Na-Hyun Lee ◽  
Kapil D. Patel ◽  
Soo-Kyung Jun ◽  
Jeong-Hui Park ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Selenium Nanoparticles ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Oxygen Species ◽  
Protective Effects ◽  
Intracellular Ros

Reactive oxygen species (ROS) are continuously produced by skeletal muscle during contractile activity and even at rest. However, the ROS generated from excessive exercise or traumatic damage may produce more ROS than can be neutralized by an antioxidant capacity, which can be harmful to muscle function. In particular, selenium is a known antioxidant that regulates physiological functions such as cell differentiation and anti-inflammatory function. In this study, we developed nano-sized antioxidative biomaterials using selenium to investigate the protective and differentiation effects against C2C12 myoblasts in an H2O2-induced oxidative stress environment. The selenium nanoparticles (SeNPs) were produced with a size of 35.6 ± 4.3 nm and showed antioxidant effects according to the 3,3′,5,5′-tetramethylbenzidine assay. Then, SeNPs were treated to C2C12 cells with or without H2O2. Our results showed that SeNPs reduced C2C12 apoptosis and intracellular ROS levels. Additionally, SeNPs effectively up-regulated in the presence of H2O2, MyoD, MyoG, α-actinin, and myosin heavy chain, which are well known to increase during myoblast differentiation as assayed by qRT-PCR, immunocytochemistry-staining, western blotting. These results demonstrate that SeNPs can accelerate differentiation with its protective effects from the ROS environment and can be applied to the treatment of skeletal muscle in a cellular redox environment.

scholarly journals Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Lei Sun ◽  
Tongsheng Chen ◽  
Xiaoping Wang ◽  
Yun Chen ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Temporal Dynamics ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
Induced Apoptosis

Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production and apoptotic cell death, demonstrated by Hoechst 33258 staining as well as flow cytometry analysis. Bax redistributed from cytosol to mitochondria from 12 to 48 h after bufalin treatment in living cells expressed with green fluorescent protein Bax. Treatment with the antioxidantN-acetyl-cysteine (NAC), a ROS scavenger, inhibited ROS generation and Bax translocation and led to a significant protection against bufalin-induced apoptosis. Our results also revealed that bufalin induced a prominent increase of caspase-3 activation blocked potently by NAC. Taken together, bufalin induced ROS-mediated Bax translocation, mitochondrial permeability transition and caspase-3 activation, implying that bufalin induced apoptosis via ROS-dependent mitochondrial death pathway in ASTC-a-1 cells.

Effect of prior chronic contractile activity on mitochondrial function and apoptotic protein expression in denervated muscle

2008 ◽  
Vol 105 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Michael F. N. O'Leary ◽  
David A. Hood
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Reactive Oxygen Species Production ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Chronic Stimulation ◽  
Apoptotic Protein ◽  
Species Production

Skeletal muscle is highly adaptable in response to increases and decreases in contractile activity. The purpose of this study was to determine whether the preconditioning of skeletal muscle has a protective effect against subsequent denervation-induced apoptotic protein expression. To investigate this, we chronically stimulated the tibialis anterior and extensor digitorum longus muscles for 7 days (10 Hz, 3 h/day) before 7 days of denervation. Denervation reduced total cytochrome- c oxidase activity by 39%, which was likely a consequence of a decrease in subsarcolemmal (SS) mitochondria. This decrease in the SS subfraction was prevented by prior chronic stimulation and, as a result, maintained total mitochondrial content at control levels. The expression of Bax was elevated 2.2-fold by denervation, and prior chronic stimulation did not attenuate this increase. This produced a increase in the Bax-to-Bcl-2 ratio, indicating greater muscle apoptotic susceptibility. Denervation also decreased state 3 respiration in SS and intermyofibrillar mitochondria and elevated state 4 reactive oxygen species production within both mitochondrial subfractions. These changes were not prevented by prior chronic stimulation. Furthermore, the antioxidant protein MnSOD was also reduced by denervation, whereas Beclin-1 was markedly elevated. This suggests that autophagic cell death could also play a significant part in denervation-induced muscle atrophy. Thus, despite prior chronic stimulation, denervation increases the apoptotic susceptibility of skeletal muscle by altering the Bax-to-Bcl-2 ratio, by increasing reactive oxygen species production, and by reducing the expression of MnSOD. Whether a more extensive stimulation paradigm would be more effective in attenuating apoptosis before muscle disuse remains to be determined.

Mitochondrial metabolic suppression and reactive oxygen species production in liver and skeletal muscle of hibernating thirteen-lined ground squirrels

2012 ◽  
Vol 302 (1) ◽  
pp. R15-R28 ◽  
Author(s):  
Jason C. L. Brown ◽  
Dillon J. Chung ◽  
Kathleen R. Belgrave ◽  
James F. Staples
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Reactive Oxygen ◽  
Substrate Oxidation ◽  
Ground Squirrels ◽  
Complex Iii ◽  
Ros Production ◽  
Oxygen Species ◽  
Skeletal Muscle Mitochondria ◽  
Species Production

During hibernation, animals cycle between periods of torpor, during which body temperature (Tb) and metabolic rate (MR) are suppressed for days, and interbout euthermia (IBE), during which Tb and MR return to resting levels for several hours. In this study, we measured respiration rates, membrane potentials, and reactive oxygen species (ROS) production of liver and skeletal muscle mitochondria isolated from ground squirrels ( Ictidomys tridecemlineatus ) during torpor and IBE to determine how mitochondrial metabolism is suppressed during torpor and how this suppression affects oxidative stress. In liver and skeletal muscle, state 3 respiration measured at 37°C with succinate was 70% and 30% lower, respectively, during torpor. In liver, this suppression was achieved largely via inhibition of substrate oxidation, likely at succinate dehydrogenase. In both tissues, respiration by torpid mitochondria further declined up to 88% when mitochondria were cooled to 10°C, close to torpid Tb. In liver, this passive thermal effect on respiration rate reflected reduced activity of all components of oxidative phosphorylation (substrate oxidation, phosphorylation, and proton leak). With glutamate + malate and succinate, mitochondrial free radical leak (FRL; proportion of electrons leading to ROS production) was higher in torpor than IBE, but only in liver. With succinate, higher FRL likely resulted from increased reduction state of complex III during torpor. With glutamate + malate, higher FRL resulted from active suppression of complex I ROS production during IBE, which may limit ROS production during arousal. In both tissues, ROS production and FRL declined with temperature, suggesting ROS production is also reduced during torpor by passive thermal effects.

scholarly journals Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1616
Author(s):  
Abdul Mannan ◽  
Zacary P Germon ◽  
Janis Chamberlain ◽  
Jonathan R Sillar ◽  
Brett Nixon ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Therapeutic Approaches ◽  
T Lymphoblasts

Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL.

scholarly journals Reactive Oxygen Species in Skeletal Muscle Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Elena Barbieri ◽  
Piero Sestili
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Contractile Activity ◽  
Reactive Oxygen ◽  
Target Cells ◽  
Past Century ◽  
Oxygen Species ◽  
Toxic Species ◽  
Dynamic Scenario

Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a “positive” or “negative” response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of “physiologically compatible” levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle.

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