Red and Infrared Low-Level Laser Therapy Prior to Injury with or without Administration after Injury Modulate Oxidative Stress during the Muscle Repair Process

IntroductionMuscle injury is common among athletes and amateur practitioners of sports. Following an injury, the production of reactive oxygen species (ROS) occurs, which can harm healthy muscle fibers (secondary damage) and delay the repair process. Low-level laser therapy (LLLT) administered prior to or following an injury has demonstrated positive and protective effects on muscle repair, but the combination of both administration times together has not been clarified.AimTo evaluate the effect of LLLT (660 nm and 780 nm, 10 J/cm², 40 mW, 3.2 J) prior to injury with or without the administration after injury on oxidative stress during the muscle repair process.MethodsWistar rats were divided into following groups: control; muscle injury alone; LLLT 660 nm + injury; LLLT 780 nm + injury; LLLT 660 nm before and after injury; and LLLT 780 nm before and after injury. The rats were euthanized on days 1, 3 and 7 following cryoinjury of the tibialis anterior (TA) muscle, which was then removed for analysis.ResultsLipid peroxidation decreased in the 660+injury group after one day. Moreover, red and infrared LLLT employed at both administration times induced a decrease in lipid peroxidation after seven days. CAT activity was altered by LLLT in all periods evaluated, with a decrease after one day in the 780+injury+780 group and after seven days in the 780+injury group as well as an increase in the 780+injury and 780+injury+780 groups after three days. Furthermore, increases in GPx and SOD activity were found after seven days in the 780+injury+780 group.ConclusionThe administration of red and infrared laser therapy at different times positively modulates the activity of antioxidant enzymes and reduces stress markers during the muscle repair process.     

EGFR-Aurka Signaling Rescues Polarity and Regeneration Defects in Dystrophin-Deficient Muscle Stem Cells by Increasing Asymmetric Divisions

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Oxidative Stress,Inflammation, and Diabetic Vasculopathies: The Role of Alpha Tocopherol Therapy

The diabetic state confers an increased propensity to accelerated atherogenesis. In addition to the established risk factors, there is evidence for increased oxidative stress and inflammation in diabetes. Increased oxidative stress is manifested by increased lipid peroxidation (e.g. increased F 2 -isoprostanes) and increased DNA damage. Evidence for increased inflammation includes increased monocyte superoxide and pro-inflammatory cytokine release (IL-1, IL-6, and TNF- &#102 ), increased monocyte adhesion to endothelium and increased levels of plasma C-reactive protein, the prototypic marker of inflammation. Most importantly, alpha tocopherol therapy, especially at high doses, clearly shows a benefit with regards to LDL oxidation, isoprostanes and a decrease in inflammatory markers such as C-reactive protein, pro-inflammatory cytokines and PAI-1 levels. Thus, it appears that, in diabetes, alpha tocopherol therapy could emerge as an additional therapeutic modality.     

Oxidative Stress (Glutathionylation) and Na,K-ATPase Activity in Rat Skeletal Muscle

Background

Changes in ion distribution across skeletal muscle membranes during muscle activity affect excitability and may impair force development. These changes are counteracted by the Na,K-ATPase. Regulation of the Na,K-ATPase is therefore important for skeletal muscle function. The present study investigated the presence of oxidative stress (glutathionylation) on the Na,K-ATPase in rat skeletal muscle membranes.

Results

Immunoprecipitation with an anti-glutathione antibody and subsequent immunodetection of Na,K-ATPase protein subunits demonstrated 9.0±1.3% and 4.1±1.0% glutathionylation of the α isoforms in oxidative and glycolytic skeletal muscle, respectively. In oxidative muscle, 20.0±6.1% of the β1 units were glutathionylated, whereas 14.8±2.8% of the β2-subunits appear to be glutathionylated in glycolytic muscle. Treatment with the reducing agent dithiothreitol (DTT, 1 mM) increased the in vitro maximal Na,K-ATPase activity by 19% (P<0.05) in membranes from glycolytic muscle. Oxidized glutathione (GSSG, 0–10 mM) increased the in vitro glutathionylation level detected with antibodies, and decreased the in vitro maximal Na,K-ATPase activity in a dose-dependent manner, and with a larger effect in oxidative compared to glycolytic skeletal muscle.

Conclusion

This study demonstrates the existence of basal glutathionylation of both the α and the β units of rat skeletal muscle Na,K-ATPase. In addition, the study suggests a negative correlation between glutathionylation levels and maximal Na,K-ATPase activity.

Perspective

Glutathionylation likely contributes to the complex regulation of Na,K-ATPase function in skeletal muscle. Especially, glutathionylation induced by oxidative stress may have a role in Na,K-ATPase regulation during prolonged muscle activity.     

Nrf2 Activates Augmenter of Liver Regeneration (ALR) via Antioxidant Response Element and Links Oxidative Stress to Liver Regeneration

Liver regeneration can be impaired by permanent oxidative stress and activation of nuclear factor erythroid 2–related factor 2 (Nrf2), known to regulate the cellular antioxidant response, and has been shown to improve the process of liver regeneration. A variety of factors regulate hepatic tissue regeneration, among them augmenter of liver regeneration (ALR), attained great attention as being survival factors for the liver with proproliferative and antiapoptotic properties. Here we determined the Nrf2/antioxidant response element (ARE) regulated expression of ALR and show ALR as a target gene of Nrf2 in vitro and in vivo. The ALR promoter comprises an ARE binding site and, therefore, ALR expression can be induced by ARE-activator tertiary butylhydroquinone (tBHQ) in hepatoma cells and primary human hepatocytes (PHH). Promoter activity and expression of ALR were enhanced after cotransfection of Nrf2 compared with control and dominant negative mutant of Nrf2. Performing partial hepatectomy in livers from Nrf2^+/+ mice compared with Nrf2^−/− knock-out (KO) mice, we found increased expression of ALR in addition to known antioxidant ARE-regulated genes. Furthermore, we observed increased ALR expression in hepatitis B virus (HBV) compared with hepatitis C virus (HCV) positive hepatoma cells and PHH. Recently, it was demonstrated that HBV infection activates Nrf2 and, now, we add results showing increased ALR expression in liver samples from patients infected with HBV. ALR is regulated by Nrf2, acts as a liver regeneration and antioxidative protein and, therefore, links oxidative stress to hepatic regeneration to ensure survival of damaged cells.     

Spectroscopic and histological evaluation of wound healing progression following Low Level Laser Therapy (LLLT)

The present study focuses on the evaluation of the effect of He‐Ne laser on tissue regeneration by monitoring collagen synthesis in wound granulation tissues in Swiss albino mice using analysis of laser induced fluorescence (LIF) and light microscopy techniques. The spectral analyses of the wound granulation tissues have indicated a dose dependent increase in collagen levels during the post‐wounding days. The histological examinations on the other hand have also shown a significant increase in collagen deposition along with the reduced edema, leukocytes, increased granulation tissue, and fibroblast number in the optimal laser dose treated group compared to the non‐illuminated controls. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Oxidative Stress and Inflammation in Brain Aging: Nutritional Considerations

Aging can be defined as the condition where stressors are not counteracted by protective functions, leading to a dysregulation in development. These changes can be translated into decrements in neuronal functioning accompanied by behavioral declines, such as decreases in motor and cognitive performance, in both humans and animals. When coupled with genetic alterations, the ultimate expression of these changes is seen in diseases such as Alzheimer disease (AD). This association will be discussed in the last section of this chapter. In this review we will describe motor and cognitive deficits in behavior due to aging, and show how these deficits are related to increased vulnerability to oxidative stress, inflammation or signaling. Importantly, using muscarinic receptors as examples, we will also try to show that the sensitivity to these insults may be differentially expressed among neurotransmitter receptor subtypes.     

Aging,Stem Cells and Tissue Regeneration: Lessons from Muscle

With age, there is a gradual decline in the regenerative properties of most tissues due to a combination of age-dependent changes in tissue-specific stem cells and in the environmental cues that promote those cells to participate in tissue maintenance and repair. In adult skeletal muscle, where the resident dedicated stem cells (“satellite cells”) are capable of rapid and highly effective regeneration in response to injury, there is just such a loss of regenerative potential with age. Satellite cell activation and cell fate determination are controlled by the Notch signaling pathway that is initiated by the rapid increase in expression of the Notch ligand, Delta, following injury. In old muscle, this upregulation of Delta is blunted and thus satellite cell activation is markedly diminished. However, by indirectly inducing Notch activity, the regenerative potential of aged satellite cells can be restored. Furthermore, exposure of aged satellite cells to serum from young mice, either in vivo by heterochronic parabiotic pairings or in vitro, rejuvenates the satellite cell response. This restorative potential suggests that tissue-specific stem cells do not lose their ability to participate in tissue maintenance and repair. Therefore, it may be that even very old stem cells may be capable of maintaining and repairing aged tissues if provided with optimal environmental cues.     

Effects of Fetal Bovine Serum on Ferrous Ion-Induced Oxidative Stress in Pheochromocytoma (PC12) Cells

Ferrous ion (Fe²⁺) has been considered to be a cause of neuronal oxidative injury. Since body fluids contain protein and serum is an essential component of tissue culture medium, we have examined the role of serum protein on Fe²⁺-mediated oxidative stress using PC12 cells and rat cerebral cortices. Fe²⁺ or the combination of ascorbate and Fe²⁺ increased concentrations of thiobarbituric acid reactive substances (TBARS) in PC12 cells and cerebrocortical homogenates in medium (RPMI 1640), but did not increase TBARS when the medium was supplemented with 10% fetal bovine serum. Treatment with ascorbate/Fe²⁺ in serum-free medium reduced endogenous glutathione (GSH) concentration in PC12 cells. However, the medium supplemented with serum did not reduce GSH concentrations. PC12 cell death induced by ascorbate/Fe²⁺ was alleviated by increasing serum or bovine albumin concentrations in the medium. These observations indicated that oxidative injury caused by the transition metal ion could be lessened by adding fetal bovine serum to culture medium.     

Relationships between Inflammation,Adiponectin, and Oxidative Stress in Metabolic Syndrome

Metabolic syndrome (MS) represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72). The control group (n = 105) comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), adiponectin, an oxidative stress marker (malondialdehyde), and antioxidant enzymes activities [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L), or IL-6 (≥1.50 pg/mL) or a lower level of adiponectin (<7.90 µg/mL) were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.     

Demographic Responses to Oxidative Stress and Inflammation in the Wandering Albatross (Diomedea exulans)

One of the major challenges in ecological research is the elucidation of physiological mechanisms that underlie the demographic traits of wild animals. We have assessed whether a marker of plasma oxidative stress (TBARS) and plasma haptoglobin (protein of the acute inflammatory phase response) measured at time t predict five demographic parameters (survival rate, return rate to the breeding colony, breeding probability, hatching and fledging success) in sexually mature wandering albatrosses over the next four years (Diomedea exulans) using a five-year individual-based dataset. Non-breeder males, but not females, having higher TBARS at time t had reduced future breeding probabilities; haptoglobin was not related to breeding probability. Neither TBARS nor haptoglobin predicted future hatching or fledging success. Haptoglobin had a marginally positive effect on female survival rate, while TBARS had a marginally negative effect on return rate. Our findings do not support the role for oxidative stress as a constraint of future reproductive success in the albatross. However, our data point to a potential mechanism underlying some aspects of reproductive senescence and survival. Our results also highlight that the study of the consequences of oxidative stress should consider the life-cycle stage of an individual and its reproductive history.     

Oxidative Stress Induces Caveolin 1 Degradation and Impairs Caveolae Functions in Skeletal Muscle Cells

Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H₂O₂) at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H₂O₂ treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H₂O₂ treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H₂O₂ treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H₂O₂ decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.     

Role of ALADIN in Human Adrenocortical Cells for Oxidative Stress Response and Steroidogenesis

Triple A syndrome is caused by mutations in AAAS encoding the protein ALADIN. We investigated the role of ALADIN in the human adrenocortical cell line NCI-H295R1 by either over-expression or down-regulation of ALADIN. Our findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore we demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, we show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. We conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting our knock-down cell model as an important in-vitro tool for studying the adrenal phenotype in triple A syndrome.     

Impact of Selenium Deficiency on Inflammation,Oxidative Stress,and Phagocytosis in Mouse Macrophages

Biological Trace Element Research - Although it has been reported that selenium (Se) deficiency can trigger inflammation, however, there are few reports on the effect of Se on the function of mouse...     

Atorvastatin Decreases Bone Loss,Inflammation and Oxidative Stress in Experimental Periodontitis

The aim of this study is to determine the effects of Atorvastatin treatment, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, in periodontal disease. Male Wistar albino rats were randomly divided into five groups of ten rats each: (1) non-ligated treatment (NL), (2) ligature only (L), (3) ligature plus 1 mg/kg Atorvastatin daily for 10 days, (4) ligature plus 5 mg/kg Atorvastatin daily for 10 days, and (5) ligature plus 10 mg/kg Atorvastatin daily for 10 days. Following the treatment course, the periodontal tissue of the animals was analyzed by Measurement of alveolar bone loss, Histopathology and immunohistochemistry to determine of the expression of COX-2, MMP-2, MMP9, and RANKL/RANK/OPG. ELISA assay was used to quantitate the levels of IL-1β, IL-10, TNF-α, myeloperoxidase, malondialdehyde, and glutathione. The periodontal group treated with 10 mg/kg of Atorvastatin (3.9±0.9 mm; p<0.05) showed reverse the alveolar bone loss caused Experimental Periodontal Disease compared to (L) (7.02±0.17 mm). The periodontal group treated with 10 mg/kg of Atorvastatin showed a significant reduction in MPO and MDA (p<0.05) compared to ligature only group (L). Similarly in this group, the levels of the proinflammatory cytokines IL-1β and TNF-α were significantly decreased (p<0.05). Furthermore, MMP-2, MMP-9, RANKL/RANK, and COX-2 were all downregulated by Atorvastatin treatment, while OPG expression was increased. The findings support a role of Atorvastatin for reducing the bone loss, inflammatory response, oxidative stress, and expression of extracellular matrix proteins, while reducing RANK/RANKL and increase OPG in periodontal disease.     

Effect of Oxidative Stress on the Expression of Thin Filament-Associated Proteins in Gastric Smooth Muscle Cells

Thin filament-associated proteins such as calponin, caldesmon, and smoothelin are believed to regulate acto-myosin interaction and thus, muscle contraction. Oxidative stress has been found to affect the normal contractile behavior of smooth muscle and is involved in the pathogenesis of a number of human diseases such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the expression of smooth muscle contractile proteins. The aim of the current study is to investigate the effect of oxidative stress on the expression of thin filament-associated proteins in rat gastric smooth muscle. Single smooth muscle cells of the stomach obtained from Sprague–Dawley rats were used. Muscle cells were treated with hydrogen peroxide (H₂O₂) (500 μM) for 30 min or the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) (1 mM) for 90 min to induce oxidative stress. Calponin, caldesmon, and smoothelin expressions were measured via specifically designed enzyme-linked immunosorbent assay. We found that exposure to exogenous H₂O₂ or incubation of dispersed gastric muscle cells with SIN-1 significantly increased the expression of calponin, caldesmon, and smoothelin proteins. In conclusion: oxidative stress increases the expression of thin filament-associated proteins in gastric smooth muscle, suggesting an important role in gastrointestinal motility disorders associated with oxidative stress.     

Overexpression of Alternative Oxidase Gene Confers Aluminum Tolerance by Altering the Respiratory Capacity and the Response to Oxidative Stress in Tobacco Cells

Aluminum (Al) stress represses mitochondrial respiration and produces reactive oxygen species (ROS) in plants. Mitochondrial alternative oxidase (AOX) uncouples respiration from mitochondrial ATP production and may improve plant performance under Al stress by preventing excess accumulation of ROS. We tested respiratory changes and ROS production in isolated mitochondria and whole cell of tobacco (SL, ALT 301) under Al stress. Higher capacities of AOX pathways relative to cytochrome pathways were observed in both isolated mitochondria and whole cells of ALT301 under Al stress. AOX1 when studied showed higher AOX1 expression in ALT 301 than SL cells under stress. In order to study the function of tobacco AOX gene under Al stress, we produced transformed tobacco cell lines by introducing NtAOX1 expressed under the control of the cauliflower mosaic virus (CaMV) 35 S promoter in sensitive (SL) Nicotiana tabacum L. cell lines. The enhancement of endogenous AOX1 expression and AOX protein with or without Al stress was in the order of transformed tobacco cell lines > ALT301 > wild type (SL). A decreased respiratory inhibition and reduced ROS production with a better growth capability were the significant features that characterized AOX1 transformed cell lines under Al stress. These results demonstrated that AOX plays a critical role in Al stress tolerance with an enhanced respiratory capacity, reducing mitochondrial oxidative stress burden and improving the growth capability in tobacco cells.