Oxidative stress and muscle homeostasis

Purpose of review The term oxidative stress is often used to indicate a condition in which the accumulation of reactive oxygen species is considered just damaging. We will discuss both the physiological and pathological role of oxidative stress on skeletal muscle homeostasis and function, and how oxidative stress can activates opposite signaling molecule to regulate gene and protein expression to guarantee muscle adaptation and to trigger a pathological condition. Recent findings Emerging evidences have assigned a critical role to oxidative stress in muscle homeostasis and in the physiopathology of skeletal muscle, suggesting that reactive oxygen species are not merely damaging agent inflicting random destruction to the cell structure and function, but useful signaling molecules to regulate growth, proliferation, differentiation, and adaptation, at least within physiological concentration. Summary The role of oxidative stress on muscle homeostasis is quite complex. It is clear that transiently increased levels of oxidative stress might reflect a potentially health promoting process, whereas an uncontrolled accumulation of oxidative stress might have pathological implication. Additional work is, therefore, necessary to understand and define precisely whether the manipulation of the redox balance represents a useful approach in the design of therapeutic strategies for muscle diseases.PURPOSE OF REVIEW: The term oxidative stress is often used to indicate a condition in which the accumulation of reactive oxygen species is considered just damaging. We will discuss both the physiological and pathological role of oxidative stress on skeletal muscle homeostasis and function, and how oxidative stress can activates opposite signaling molecule to regulate gene and protein expression to guarantee muscle adaptation and to trigger a pathological condition. RECENT FINDINGS: Emerging evidences have assigned a critical role to oxidative stress in muscle homeostasis and in the physiopathology of skeletal muscle, suggesting that reactive oxygen species are not merely damaging agent inflicting random destruction to the cell structure and function, but useful signaling molecules to regulate growth, proliferation, differentiation, and adaptation, at least within physiological concentration. SUMMARY: The role of oxidative stress on muscle homeostasis is quite complex. It is clear that transiently increased levels of oxidative stress might reflect a potentially health promoting process, whereas an uncontrolled accumulation of oxidative stress might have pathological implication. Additional work is, therefore, necessary to understand and define precisely whether the manipulation of the redox balance represents a useful approach in the design of therapeutic strategies for muscle diseases

Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response.

Adipocytes promote cancer progression and impair treatment, and have been shown to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we investigate whether this protection is mediated by changes in oxidative stress. Co-culture experiments showed that adipocytes protect ALL cells from oxidative stress induced by drugs or irradiation. We demonstrated that ALL cells induce intracellular ROS and an oxidative stress response in adipocytes. This adipocyte oxidative stress response leads to the secretion of soluble factors which protect ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL cells elicit an oxidative stress response in adipocytes, leading to adipocyte protection of ALL cells against DNR

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2

Trolox and ascorbic acid reduce direct and indirect oxidative stress in the IPEC-J2 cells, an in vitro model for the porcine gastrointestinal tract

Oxidative stress in the small intestinal epithelium is a major cause of barrier malfunction and failure to regenerate. This study presents a functional in vitro model using the porcine small intestinal epithelial cell line IPEC-J2 to examine the effects of oxidative stress and to estimate the antioxidant and regenerative potential of Trolox, ascorbic acid and glutathione monoethyl ester. Hydrogen peroxide and diethyl maleate affected the tight junction (zona occludens-1) distribution, significantly increased intracellular oxidative stress (CM-H(2)DCFDA) and decreased the monolayer integrity (transepithelial electrical resistance and FD-4 permeability), viability (neutral red) and wound healing capacity (scratch assay). Trolox (2 mM) and 1 mM ascorbic acid pre-treatment significantly reduced intracellular oxidative stress, increased wound healing capacity and reduced FD-4 permeability in oxidatively stressed IPEC-J2 cell monolayers. All antioxidant pre-treatments increased transepithelial electrical resistance and viability only in diethyl maleate-treated cells. Glutathione monoethyl ester (10 mM) pretreatment significantly decreased intracellular oxidative stress and monolayer permeability only in diethyl maleate-treated cells. These data demonstrate that the IPEC-J2 oxidative stress model is a valuable tool to screen antioxidants before validation in piglets

Assessment of Oxidative Stress in Peste Des Petits Ruminants (Ovine Rinderpest) Affected Goats

The aim of the present investigation was to evaluate oxidative stress in goats affected with peste des petits ruminants (PPR). The experiment was designed to collect blood samples from PPR affected as well as healthy goats during a series of PPR outbreaks which occurred during February to April 2012 in different districts of Rajasthan state (India). Out of total 202 goats of various age groups and of both the sexes, 155 goats were PPR affected and 47 were healthy. Oxidative stress was evaluated by determining various serum biomarkers viz. vitamin A, vitamin C, vitamin E, glutathione, catalase, superoxide dismutase, glutathione reductase and xanthine oxidase, the mean values of which were 1.71±0.09 µmol L-1, 13.02±0.14 µmol L-1, 2.22±0.09 µmol L-1, 3.03±0.07 µmol L-1, 135.12±8.10 kU L-1, 289.13±8.00 kU L-1, 6.11± 0.06 kU L-1 and 98.12±3.12 mU L-1, respectively. Each parameter analysis of variance showed highly significant effect (P=0.0001) of health status and age category. Further interaction between health status and age category was also highly significant (P=0.0001) for each parameter studied. The results indicated that vitamins A, C, E and glutathione levels depressed by 18.95%, 38.67%, 47.64%, and 47.39%, respectively and the serum catalase, superoxide dismutase, glutathione reductase and xanthine oxidase activities increased by 90.79%, 75.11%, 90.34%, and 44.06%, respectively in affected animals as compared to that in healthy ones. On the basis of the altered levels of serum biomarkers of oxidative stress it was concluded that the animals affected with PPR developed oxidative stress

Cytokinin response factor 6 represses cytokinin-associated genes during oxidative stress

Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6-dependent genes and establishes a novel connection between cytokinin and oxidative stress response

Plasma total antioxidant capacity and peroxidation biomarkers in psoriasis

Systemic biomarkers of oxidative stress can be relevant for assessment of psoriasis severity, for prediction of the outcome of therapy and of the development of comorbidities. In this review we aimed to evaluate the relationship between plasma total antioxidant capacity (TAC) and peroxidation biomarkers, as well as their association with dyslipidemia and systemic inflammation in psoriasis. The review of 59 case–control comparisons (from 41 studies) and 17 interventions (from 13 studies) suggests that peroxidation markers are more sensitive than TAC in the evaluation of oxidative stress in psoriasis. Although few studies investigated the effect of treatment on oxidative stress, it seems that biological drugs could be the better choice in the treatment of psoriasis. However, considering the limitations of TAC and plasma peroxidation markers, this review suggests that new methods should be developed in order to evaluate systemic oxidative stress in psoriasis

Does oxidative stress shorten telomeres in vivo? A review

The length of telomeres, the protective caps of chromosomes, is increasingly used as a biomarker of individual health state because it has been shown to predict chances of survival in a range of endothermic species including humans. Oxidative stress is presumed to be a major cause of telomere shortening, but most evidence to date comes from in vitro cultured cells. The importance of oxidative stress as a determinant of telomere shortening in vivo remains less clear and has recently been questioned. We, therefore, reviewed correlative and experimental studies investigating the links between oxidative stress and telomere shortening in vivo. While correlative studies provide equivocal support for a connection between oxidative stress and telomere attrition (10 of 18 studies), most experimental studies published so far (seven of eight studies) partially or fully support this hypothesis. Yet, this link seems to be tissue-dependent in some cases, or restricted to particular categories of individual (e.g. sex-dependent) in other cases. More experimental studies, especially those decreasing antioxidant protection or increasing pro-oxidant generation, are required to further our understanding of the importance of oxidative stress in determining telomere length in vivo. Studies comparing growing versus adult individuals, or proliferative versus non-proliferative tissues would provide particularly important insights

A comparison of melatonin and α-lipoic acid in the induction of antioxidant defences in L6 rat skeletal muscle cells.

Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid