206,412 research outputs found

    Cytosolic redox components regulate protein homeostasis via additional localisation in the mitochondrial intermembrane space

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    Oxidative protein folding is confined to the bacterial periplasm, endoplasmic reticulum and the mitochondrial intermembrane space. Maintaining a redox balance requires the presence of reductive pathways. The major thiol-reducing pathways engage the thioredoxin and the glutaredoxin systems which are involved in removal of oxidants, protein proofreading and folding. Alterations in redox balance likely affect the flux of these redox pathways and are related to ageing and diseases such as neurodegenerative disorders and cancer. Here, we first review the well-studied oxidative and reductive processes in the bacterial periplasm and the endoplasmic reticulum, and then discuss the less understood process in the mitochondrial intermembrane space, highlighting its importance for the proper function of the cell

    Oxidative stress and muscle homeostasis

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    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

    Syntaphilin controls a mitochondrial rheostat for proliferation-motility decisions in cancer.

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    Tumors adapt to an unfavorable microenvironment by controlling the balance between cell proliferation and cell motility, but the regulators of this process are largely unknown. Here, we show that an alternatively spliced isoform of syntaphilin (SNPH), a cytoskeletal regulator of mitochondrial movements in neurons, is directed to mitochondria of tumor cells. Mitochondrial SNPH buffers oxidative stress and maintains complex II-dependent bioenergetics, sustaining local tumor growth while restricting mitochondrial redistribution to the cortical cytoskeleton and tumor cell motility. Conversely, introduction of stress stimuli to the microenvironment, including hypoxia, acutely lowered SNPH levels, resulting in bioenergetics defects and increased superoxide production. In turn, this suppressed tumor cell proliferation but increased tumor cell invasion via greater mitochondrial trafficking to the cortical cytoskeleton. Loss of SNPH or expression of an SNPH mutant lacking the mitochondrial localization sequence resulted in increased metastatic dissemination in xenograft or syngeneic tumor models in vivo. Accordingly, tumor cells that acquired the ability to metastasize in vivo constitutively downregulated SNPH and exhibited higher oxidative stress, reduced cell proliferation, and increased cell motility. Therefore, SNPH is a stress-regulated mitochondrial switch of the cell proliferation-motility balance in cancer, and its pathway may represent a therapeutic target

    Hypoxia-Induced Oxidative Stress Modulation with Physical Activity.

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    Increased oxidative stress, defined as an imbalance between prooxidants and antioxidants, resulting in molecular damage and disruption of redox signaling, is associated with numerous pathophysiological processes and known to exacerbate chronic diseases. Prolonged systemic hypoxia, induced either by exposure to terrestrial altitude or a reduction in ambient O2 availability is known to elicit oxidative stress and thereby alter redox balance in healthy humans. The redox balance modulation is also highly dependent on the level of physical activity. For example, both high-intensity exercise and inactivity, representing the two ends of the physical activity spectrum, are known to promote oxidative stress. Numerous to-date studies indicate that hypoxia and exercise can exert additive influence upon redox balance alterations. However, recent evidence suggests that moderate physical activity can attenuate altitude/hypoxia-induced oxidative stress during long-term hypoxic exposure. The purpose of this review is to summarize recent findings on hypoxia-related oxidative stress modulation by different activity levels during prolonged hypoxic exposures and examine the potential mechanisms underlying the observed redox balance changes. The paper also explores the applicability of moderate activity as a strategy for attenuating hypoxia-related oxidative stress. Moreover, the potential of such moderate intensity activities used to counteract inactivity-related oxidative stress, often encountered in pathological, elderly and obese populations is also discussed. Finally, future research directions for investigating interactive effects of altitude/hypoxia and exercise on oxidative stress are proposed

    Modulation of the oxidative stress and lipid peroxidation by endocannabinoids and their lipid analogues

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    Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes. In this scenario, a link between the endocannabinoid system (ECS) and redox homeostasis impairment appears to be crucial. Anandamide and 2-arachidonoylglycerol, the best characterized endocannabinoids, are able to modulate the activity of several antioxidant enzymes through targeting the cannabinoid receptors type 1 and 2 as well as additional receptors such as the transient receptor potential vanilloid 1, the peroxisome proliferator-activated receptor alpha, and the orphan G protein-coupled receptors 18 and 55. Moreover, the endocannabinoids lipid analogues N-acylethanolamines showed to protect cell damage and death from reactive aldehydes-induced oxidative stress by restoring the intracellular oxidants-antioxidants balance. In this review, we will provide a better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts

    Differences in the oxidative balance of dispersing and non-dispersing individuals: an experimental approach in a passerine bird.

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    Dispersal is often associated with a suite of phenotypic traits that might reduce dispersal costs, but can be energetically costly themselves outside dispersal. Hence, dispersing and philopatric individuals might differ throughout their life cycle in their management of energy production. Because higher energy expenditure can lead to the production of highly reactive oxidative molecules that are deleterious to the organism if left uncontrolled, dispersing and philopatric individuals might differ in their management of oxidative balance. Here, we experimentally increased flight costs during reproduction via a wing load manipulation in female collared flycatchers (Ficedula albicollis) breeding in a patchy population. We measured the effects of the manipulation on plasmatic markers of oxidative balance and reproductive success in dispersing and philopatric females. The impact of the wing load manipulation on the oxidative balance differed according to dispersal status. The concentration of reactive oxygen metabolites (ROMs), a marker of pro-oxidant status, was higher in philopatric than dispersing females in the manipulated group only. Differences between dispersing and philopatric individuals also depended on habitat quality, as measured by local breeding density. In low quality habitats, ROMs as well as nestling body mass were higher in philopatric females compared to dispersing ones. Independently of the manipulation or of habitat quality, plasma antioxidant capacity differed according to dispersal status: philopatric females showed higher antioxidant capacity than dispersing ones. Nestlings raised by philopatric females also had a higher fledging success. Our results suggest that dispersing individuals maintain a stable oxidative balance when facing challenging environmental conditions, at the cost of lower reproductive success. Conversely, philopatric individuals increase their effort, and thus oxidative costs, in challenging conditions thereby maintaining their reproductive success. Our study sheds light on energetics and oxidative balance as possible processes underlying phenotypic differences between dispersing and philopatric individuals

    Experimental inhibition of a key cellular antioxidant affects vocal communication

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    1. There is substantial interest of evolutionary ecologists in the proximate mechanisms that modulate vocal communication. In recent times, there has been growing interest in the role of oxidative stress as a mediator of avian song expression. 2. Here, we tested whether the experimental inhibition of the synthesis of a key cellular antioxidant (glutathione) reduces song rate metrics of male European starlings (Sturnus vulgaris). We measured the effect of our treatment on total song rate and on its two components, undirected and nest-box-oriented song, outside the breeding season. 3. Treated males that did not own a nest-box (subordinate males likely to be of lower quality) suffered increased oxidative stress relative to untreated males, while treated males that owned a nest-box (dominant males likely to be of higher quality) did not. Treated non-owners also reduced their undirected song rate, whereas treated nest-box owners did not suffer any reduction in song rate. 4. Our results revealed that inhibition of a key cellular antioxidant results in decreased vocal communication in a social vertebrate, and that this effect is dependent on its social status (nest-box owner vs. non-owner). 5. This work provides support for the hypothesis that acoustic signals may honestly convey information about the individual oxidative status and capacity to regulate the oxidative balance. Our findings raise the possibility of hitherto unexplored impacts of oxidative stress on fitness traits in social species

    Proteome readjustments in the apoplastic space of Arabidopsis thaliana ggt1 mutant leaves exposed to UV-B radiation

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    Ultraviolet-B radiation acts as an environmental stimulus, but in high doses it has detrimental effects on plant metabolism. Plasma membranes represent a major target for ROS generated by this harmful radiation. Oxidative reactions occurring in the apoplastic space are counteracted by antioxidative systems mainly involving ascorbate and, to some extent, glutathione. The occurrence of the latter and its exact role in the extracellular space are not well documented, however. In Arabidopsis thaliana, the gamma-glutamyl transferase isoform GGT1 bound to the cell wall takes part in the so-called gamma-glutamyl cycle for extracellular glutathione degradation and recovery, and may be implicated in redox sensing and balance. In this work, oxidative conditions were imposed with UV-B and studied in redox altered ggt1 mutants. The response of ggt1 knockout Arabidopsis leaves to UV-B radiation was assessed by investigating changes in extracellular glutathione and ascorbate content and their redox state, and in apoplastic protein composition. Our results show that, on UV-B exposure, soluble antioxidants respond to the oxidative conditions in both genotypes. Rearrangements occur in their apoplastic protein composition, suggesting an involvement of H2O2, which may ultimately act as a signal. Other important changes relating to hormonal effects, cell wall remodeling, and redox activities are discussed. We argue that oxidative stress conditions imposed by UV-B and disruption of the gamma-glutamyl cycle result in similar stress-induced responses, to some degree at least. Data are available via ProteomeXchange with identifier PXD001807
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