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PubMed Central (PMC3 - NLM DTD) (3.006.812 recursos)

Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).

Antioxidants & Redox Signaling

Mostrando recursos 1 - 20 de 968

  1. Manganese Superoxide Dismutase Expression Regulates the Switch Between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma

    Loo, Ser Yue; Hirpara, Jayshree L.; Pandey, Vijay; Tan, Tuan Zea; Yap, Celestial T.; Lobie, Peter E.; Thiery, Jean Paul; Goh, Boon Cher; Pervaiz, Shazib; Clément, Marie-Véronique; Kumar, Alan Prem
    Aim: Epithelial–mesenchymal transition (EMT) is characterized by the acquisition of invasive fibroblast-like morphology by epithelial cells that are highly polarized. EMT is recognized as a crucial mechanism in cancer progression and metastasis. In this study, we sought to assess the involvement of manganese superoxide dismutase (MnSOD) during the switch between epithelial-like and mesenchymal-like phenotypes in breast carcinoma. Results: Analysis of breast carcinomas from The Cancer Genome Atlas database revealed strong positive correlation between tumors' EMT score and the expression of MnSOD. This positive correlation between MnSOD and EMT score was significant and consistent across all breast cancer subtypes. Similarly, a...

  2. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

    Campochiaro, Peter A.; Strauss, Rupert W.; Lu, Lili; Hafiz, Gulnar; Wolfson, Yulia; Shah, Syed M.; Sophie, Raafay; Mir, Tahreem A.; Scholl, Hendrik P.
    Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase...

  3. Hydrogen Sulfide Maintains Mitochondrial DNA Replication via Demethylation of TFAM

    Li, Shuangshuang; Yang, Guangdong
    Aims: Hydrogen sulfide (H2S) exerts a wide range of actions in the body, especially in the modulation of mitochondrial functions. The normal replication of mitochondrial DNA (mtDNA) is critical for cellular energy metabolism and mitochondrial biogenesis. The aim of this study was to investigate whether H2S affects mtDNA replication and the underlying mechanisms. We hypothesize that H2S maintains mtDNA copy number via inhibition of Dnmt3a transcription and TFAM promoter methylation. Results: Here, we demonstrated that deficiency of cystathionine gamma-lyase (CSE), a major H2S-producing enzyme, reduces mtDNA copy number and mitochondrial contents, and it inhibits the expressions of mitochondrial transcription factor...

  4. Peroxisomes and Kidney Injury

    Vasko, Radovan
    Significance: Peroxisomes are organelles present in most eukaryotic cells. The organs with the highest density of peroxisomes are the liver and kidneys. Peroxisomes possess more than fifty enzymes and fulfill a multitude of biological tasks. They actively participate in apoptosis, innate immunity, and inflammation. In recent years, a considerable amount of evidence has been collected to support the involvement of peroxisomes in the pathogenesis of kidney injury. Recent Advances: The nature of the two most important peroxisomal tasks, beta-oxidation of fatty acids and hydrogen peroxide turnover, functionally relates peroxisomes to mitochondria. Further support for their communication and cooperation is furnished...

  5. NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

    Diebold, Becky A.; Smith, Susan M.E.; Li, Yang; Lambeth, J. David

  6. Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2

    Carbone, Federico; Teixeira, Priscila Camillo; Braunersreuther, Vincent; Mach, François; Vuilleumier, Nicolas; Montecucco, Fabrizio

  7. Voltage-Gated Proton Channels as Novel Drug Targets: From NADPH Oxidase Regulation to Sperm Biology

    Seredenina, Tamara; Demaurex, Nicolas; Krause, Karl-Heinz

  8. NOX Modifiers—Just a Step Away from Application in the Therapy of Airway Inflammation?

    Wieczfinska, Joanna; Sokolowska, Milena; Pawliczak, Rafal

  9. Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation

    Waltz, Paul; Escobar, Daniel; Botero, Ana Maria; Zuckerbraun, Brian S.
    Significance: Nitric oxide (NO) is a critical signaling molecule marked by complex chemistry and varied biological responses depending on the context of the redox environment. In the setting of inflammation, NO can not only contribute to tissue injury and be causative of oxidative damage but can also signal as an adaptive molecule to limit inflammatory signaling in multiple cell types and tissues. Recent Advances: An advance in our understanding of NO biology was the recognition of the nitrate-nitrite-NO axis, whereby nitrate (predominantly from dietary sources) could be converted to nitrite and nitrite could be reduced to NO. Critical Issues: Intriguingly,...

  10. Mechanisms of Histone Deacetylase Inhibitor-Regulated Gene Expression in Cancer Cells

    Chueh, Anderly C.; Tse, Janson W.T.; Tögel, Lars; Mariadason, John M.
    Significance: Class I and II histone deacetylase inhibitors (HDACis) are approved for the treatment of cutaneous T-cell lymphoma and are undergoing clinical trials as single agents, and in combination, for other hematological and solid tumors. Understanding their mechanisms of action is essential for their more effective clinical use, and broadening their clinical potential. Recent Advances: HDACi induce extensive transcriptional changes in tumor cells by activating and repressing similar numbers of genes. These transcriptional changes mediate, at least in part, HDACi-mediated growth inhibition, apoptosis, and differentiation. Here, we highlight two fundamental mechanisms by which HDACi regulate gene expression—histone and transcription factor...

  11. Receptor-Independent Ectopic Activity of Prolactin Predicts Aggressive Lung Tumors and Indicates HDACi-Based Therapeutic Strategies

    Le Bescont, Aurore; Vitte, Anne-Laure; Debernardi, Alexandra; Curtet, Sandrine; Buchou, Thierry; Vayr, Jessica; de Reyniès, Aurélien; Ito, Akihiro; Guardiola, Philippe; Brambilla, Christian; Yoshida, Minoru; Brambilla, Elisabeth; Rousseaux, Sophie; Khochbin, Saadi
    Aims: Ectopic activation of tissue-specific genes accompanies malignant transformation in many cancers. Prolactin (PRL) aberrant activation in lung cancer was investigated here to highlight its value as a biomarker. Results: PRL is ectopically activated in a subset of very aggressive lung tumors, associated with a rapid fatal outcome, in our cohort of 293 lung tumor patients and in an external independent series of patients. Surprisingly PRL receptor expression was not detected in the vast majority of PRL-expressing lung tumors. Additionally, the analysis of the PRL transcripts in lung tumors and cell lines revealed systematic truncations of their 5′ regions, including the...

  12. Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure: Implications for Cancer Therapy

    Stengel, Kristy R.; Hiebert, Scott W.
    Significance: The contribution of epigenetic alterations to cancer development and progression is becoming increasingly clear, prompting the development of epigenetic therapies. Histone deacetylase inhibitors (HDIs) represent one of the first classes of such therapy. Two HDIs, Vorinostat and Romidepsin, are broad-spectrum inhibitors that target multiple histone deacetylases (HDACs) and are FDA approved for the treatment of cutaneous T-cell lymphoma. However, the mechanism of action and the basis for the cancer-selective effects of these inhibitors are still unclear. Recent Advances: While the anti-tumor effects of HDIs have traditionally been attributed to their ability to modify gene expression after the accumulation of...

  13. Targeting Histone Deacetylases in Diseases: Where Are We?

    Benedetti, Rosaria; Conte, Mariarosaria; Altucci, Lucia
    Significance: Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death. Recent Advances: Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or...

  14. Imaging Reactive Oxygen Species-Induced Modifications in Living Systems

    Maulucci, Giuseppe; Bačić, Goran; Bridal, Lori; Schmidt, Harald H.H.W.; Tavitian, Bertrand; Viel, Thomas; Utsumi, Hideo; Yalçın, A. Süha; De Spirito, Marco
    Significance: Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS. Recent Advances: Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation. New imaging techniques as well as new contrast agents in clinically established modalities were developed in the previous decade. Critical Issues: An ideal imaging technique should determine ROS changes with high spatio-temporal resolution, detect physiologically relevant...

  15. Epigenetic Upregulation of Metallothionein 2A by Diallyl Trisulfide Enhances Chemosensitivity of Human Gastric Cancer Cells to Docetaxel Through Attenuating NF-κB Activation

    Pan, Yuanming; Lin, Shuye; Xing, Rui; Zhu, Min; Lin, Bonan; Cui, Jiantao; Li, Wenmei; Gao, Jing; Shen, Lin; Zhao, Yuanyuan; Guo, Mingzhou; Wang, Ji Ming; Huang, Jiaqiang; Lu, Youyong
    Aims: Metallothionein 2A (MT2A) and nuclear factor-kappaB (NF-κB) are both involved in carcinogenesis and cancer chemosensitivity. We previously showed decreased expression of MT2A and IκB-α in human gastric cancer (GC) associated with poor prognosis of GC patients. The present study investigated the effect of diallyl trisulfide (DATS), a garlic-derived compound, and docetaxel (DOC) on regulation of MT2A in relation to NF-κB in GC cells. Results: DATS attenuated NF-κB signaling in GC cells, resulting in G2/M cell cycle arrest and apoptosis, culminating in the inhibition of cell proliferation and tumorigenesis in nude mice. The anti-GC effect of DATS was attributable to...

  16. Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)3(tpa-κ3N)]+ Against a Pathogenic Escherichia coli that Causes Urinary Infections

    Tinajero-Trejo, Mariana; Rana, Namrata; Nagel, Christoph; Jesse, Helen E.; Smith, Thomas W.; Wareham, Lauren K.; Hippler, Michael; Schatzschneider, Ulrich; Poole, Robert K.
    Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa-κ3N)]+) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. Results: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells,...

  17. Cardiolipin Signaling Mechanisms: Collapse of Asymmetry and Oxidation

    Kagan, Valerian E.; Tyurina, Yulia Y.; Tyurin, Vladimir A.; Mohammadyani, Dariush; Angeli, Jose Pedro Friedmann; Baranov, Sergei V.; Klein-Seetharaman, Judith; Friedlander, Robert M.; Mallampalli, Rama K.; Conrad, Marcus; Bayir, Hülya
    Significance: An ancient anionic phospholipid, cardiolipin (CL), ubiquitously present in prokaryotic and eukaryotic membranes, is essential for several structural and functional purposes. Recent Advances: The emerging role of CLs in signaling has become the focus of many studies. Critical Issues: In this work, we describe two major pathways through which mitochondrial CLs may fulfill the signaling functions via utilization of their (i) asymmetric distribution across membranes and translocations, leading to the surface externalization and (ii) ability to undergo oxidation reactions to yield the signature products recognizable by the executionary machinery of cells. Future Directions: We present a concept that CLs...

  18. Isolevuglandin-Type Lipid Aldehydes Induce the Inflammatory Response of Macrophages by Modifying Phosphatidylethanolamines and Activating the Receptor for Advanced Glycation Endproducts

    Guo, Lilu; Chen, Zhongyi; Amarnath, Venkataraman; Yancey, Patricia G.; Van Lenten, Brian J.; Savage, Justin R.; Fazio, Sergio; Linton, MacRae F.; Davies, Sean S.
    Aims: Increased lipid peroxidation occurs in many conditions associated with inflammation. Because lipid peroxidation produces lipid aldehydes that can induce inflammatory responses through unknown mechanisms, elucidating these mechanisms may lead to development of better treatments for inflammatory diseases. We recently demonstrated that exposure of cultured cells to lipid aldehydes such as isolevuglandins (IsoLG) results in the modification of phosphatidylethanolamine (PE). We therefore sought to determine (i) whether PE modification by isolevuglandins (IsoLG-PE) occurred in vivo, (ii) whether IsoLG-PE stimulated the inflammatory responses of macrophages, and (iii) the identity of receptors mediating the inflammatory effects of IsoLG-PE. Results: IsoLG-PE levels were...

  19. Isolevuglandin Adducts in Disease

    Salomon, Robert G.; Bi, Wenzhao
    Significance: A diverse family of lipid-derived levulinaldehydes, isolevuglandins (isoLGs), is produced by rearrangement of endoperoxide intermediates generated through both cyclooxygenase (COX) and free radical-induced cyclooxygenation of polyunsaturated fatty acids and their phospholipid esters. The formation and reactions of isoLGs with other biomolecules has been linked to alcoholic liver disease, Alzheimer's disease, age-related macular degeneration, atherosclerosis, cardiac arythmias, cancer, end-stage renal disease, glaucoma, inflammation of allergies and infection, mitochondrial dysfunction, multiple sclerosis, and thrombosis. This review chronicles progress in understanding the chemistry of isoLGs, detecting their production in vivo and understanding their biological consequences. Critical Issues: IsoLGs have never been isolated...

  20. Unbreak My Heart: Targeting Mitochondrial Autophagy in Diabetic Cardiomyopathy

    Kubli, Dieter A.; Gustafsson, Åsa B.
    Significance: Diabetes is strongly associated with increased incidence of heart disease and mortality due to development of diabetic cardiomyopathy. Even in the absence of cardiovascular disease, cardiomyopathy frequently arises in diabetic patients. Current treatment options for cardiomyopathy in diabetic patients are the same as for nondiabetic patients and do not address the causes underlying the loss of contractility. Recent Advances: Although there are numerous distinctions between Type 1 and Type 2 diabetes, recent evidence suggests that the two disease states converge on mitochondria as an epicenter for cardiomyocyte damage. Critical Issues: Accumulation of dysfunctional mitochondria contributes to cardiac tissue injury...

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