1,721,053 research outputs found

    Natural compounds as modulators of NADPH oxidases.

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    Reactive oxygen species (ROS) are cellular signals generated ubiquitously by all mammalian cells, but their relative unbalance triggers also diseases through intracellular damage to DNA, RNA, proteins, and lipids. NADPH oxidases (NOX) are the only known enzyme family with the sole function to produce ROS. The NOX physiological functions concern host defence, cellular signaling, regulation of gene expression, and cell differentiation. On the other hand, increased NOX activity contributes to a wide range of pathological processes, including cardiovascular diseases, neurodegeneration, organ failure, and cancer. Therefore targeting these enzymatic ROS sources by natural compounds, without affecting the physiological redox state, may be an important tool. This review summarizes the current state of knowledge of the role of NOX enzymes in physiology and pathology and provides an overview of the currently available NADPH oxidase inhibitors derived from natural extracts such as polyphenols

    Reactive oxygen species in stem cells

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    tem cells are defined by their unique ability to self-renew and their multipotent differentiation capacity, thus maintaining tissue homeostasis throughout the life of a multicellular organism. Stem cells reside in niches characterized by hypoxia and low reactive oxygen species (ROS), both of which are critical for maintaining the potential for self-renewal and stemness. Until recently, the focus in stem cell biology has been on the adverse effects of ROS, particularly the damaging effects of ROS accumulation on tissue aging and the development of cancer. However, it has become increasingly clear that, in some cases, redox status plays an important role in stem cell maintenance, that is, regulation of the cell cycle. In fact, ROS at low levels function as signaling molecules to mediate cell proliferation, migration, and differentiation and gene expression. ROS levels in stem and progenitor cells have a clear correlation with cellular functions and are regulated by a fine-tuning of the balance between ROS-generating and antioxidant defense systems. This special issue tries to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, which is critical to address the important role of redox homeostasis in the regulation of both self-renewal and differentiation of stem cells

    Enhancement of glucose transport in rat thymocytes by different radical sources

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    This study demonstrates that oxidative stress induced in rat thymocytes by the hydrophilic 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), the lipophilic cumene hydroperoxide (CumOOH) and the freely diffusible H2O2 is associated with an activation of facilitative glucose transport rate, mediated by GLUT1, the major transporter in this cell type. We compared the effects of the three tested radical sources on the kinetic transport parameters, showing that the transport rate enhancement in the treated cells can be ascribed to an increase in the V-max value, apart from the site of generation of the oxidative stress. The enhancement of glucose transport by the three oxidants in thymocytes was significantly attenuated both by protein tyrosine kinase inhibitors as genistein and tyrphostin A23 and by U73122, a phospholipase C inhibitor. Genistein and U73122 reversed also the cited increase of V-max values. It is concluded that the stimulation of glucose transport in response to different oxidants is mediated, at least in part, through reactive oxygen species (ROS)-induced stimulation of protein tyrosine kinase and phospholipase C pathways

    Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry.

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    The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed

    Dietary polyphenols and their effects on cell biochemistry and pathophysiology 2013

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    Dietary polyphenols, along with other natural compounds occurring in fruits and vegetables, have been reported to exert beneficial effects in a multitude of disease states, including cancer, cardiovascular disease, and neurodegenerative disorders. Many of the biological actions of polyphenols have been attributed to their antioxidant properties; however, during the last years, a new realization of how nutritional antioxidants may function has been envisaged, and recent findings have suggested that they affect several cellular pathways exerting a pleiotropic effect. This special issue analyzes and expands our knowledge on the new mechanisms of actions of polyphenols and other natural compounds with the aim to better understand what could be defined as “the network” of their different biological effects

    Nuclear redox control of stem cell ageing

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    Mesenchymal stem cells (MSCs) have emerged as an important tool that can be used for drug screening, disease modeling and tissue regeneration thanks to their easy preparation, differentiation potential and immunomodulatory activity. A redox imbalance, due to extensive culture of stem cells in vitro prior to clinical use, can lead to oxidative stress. However, oxidative stress is known to play an important role in modulating different stem cells properties, such as self-renewal, proliferation, differentiation and senescence. A specific source of reactive oxygen species, the NADPH oxidase isoform 4 (Nox4), can localize also into the nuclei where it can have an impact on the regulation of crucial stemness-related genes. Moreover, the accumulation in human MSCs’ nuclei of the nuclear lamina precursor, prelamin A, gives rise to a premature aging phenotype that ultimately causes reduced functionality of these cells in vivo. The aim of the study was to investigate the aging process occurring during in vitro expansion of human fetal MSCs, obtained from amniotic fluid at similar gestational age. This process is certainly influenced by the oxidative stress exposure implied in extensive culture, but could be also donor dependent. The analysis of 15 AFSC samples allowed to classify them in groups with different levels of stemness properties evident even since the first passages in culture. In summary, the expression of Oct-4, a pluripotency gene, and proliferation rate are inversely correlated to the presence of the nuclear form of Nox4, the content of reactive oxygen species, DNA damage signs and the onset of senescence and premature aging markers, including accumulation of prelamin A, p21 and p16. Indeed, coimmunoprecipitation experiments demonstrated an interaction between prelamin A and Nox4, suggesting an interplay of these proteins in modulating the maintenance of stemness properties
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