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PubMed Central (PMC3 - NLM DTD) (2.987.316 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 959

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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,...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Mitochondrial Dynamics in Diabetic Cardiomyopathy

    Galloway, Chad A.; Yoon, Yisang
    Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial...

  13. Protective Mechanisms of Mitochondria and Heart Function in Diabetes

    Aon, Miguel A.; Tocchetti, Carlo G.; Bhatt, Niraj; Paolocci, Nazareno; Cortassa, Sonia
    Significance: The heart depends on continuous mitochondrial ATP supply and maintained redox balance to properly develop force, particularly under increased workload. During diabetes, however, myocardial energetic-redox balance is perturbed, contributing to the systolic and diastolic dysfunction known as diabetic cardiomyopathy (DC). Critical Issues: How these energetic and redox alterations intertwine to influence the DC progression is still poorly understood. Excessive bioavailability of both glucose and fatty acids (FAs) play a central role, leading, among other effects, to mitochondrial dysfunction. However, where and how this nutrient excess affects mitochondrial and cytoplasmic energetic/redox crossroads remains to be defined in greater detail. Recent...

  14. Metabolic Alterations Induce Oxidative Stress in Diabetic and Failing Hearts: Different Pathways, Same Outcome

    Roul, David; Recchia, Fabio A.
    Significance: Several authors have proposed a link between altered cardiac energy substrate metabolism and reactive oxygen species (ROS) generation. A cogent evidence of this association has been found in diabetic cardiomyopathy (dCM); however, experimental findings in animal models of heart failure (HF) and in human myocardium also seem to support the coexistence of the two alterations in HF. Critical Issues: Two important questions remain open: whether pathological changes in metabolism play an important role in enhancing oxidative stress and whether there is a common pathway linking altered substrate utilization and activation of ROS-generating enzymes, independently of the underlying cardiac pathology....

  15. The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

    Schilling, Joel D.
    Significance: Diabetes is an important risk factor for the development of heart failure (HF). Given the increasing prevalence of diabetes in the population, strategies are needed to reduce the burden of HF in these patients. Recent Advances: Diabetes is associated with several pathologic findings in the heart including dysregulated metabolism, lipid accumulation, oxidative stress, and inflammation. Emerging evidence suggests that mitochondrial dysfunction may be a central mediator of these pathologic responses. The development of therapeutic approaches targeting mitochondrial biology holds promise for the management of HF in diabetic patients. Critical Issues: Despite significant data implicating mitochondrial pathology in diabetic cardiomyopathy,...

  16. Functional Crosstalk Between Lysine Methyltransferases on Histone Substrates: The Case of G9A/GLP and Polycomb Repressive Complex 2

    Mozzetta, Chiara; Pontis, Julien; Ait-Si-Ali, Slimane
    Significance: Methylation of histone H3 on lysine 9 and 27 (H3K9 and H3K27) are two epigenetic modifications that have been linked to several crucial biological processes, among which are transcriptional silencing and cell differentiation. Recent Advances: Deposition of these marks is catalyzed by H3K9 lysine methyltransferases (KMTs) and polycomb repressive complex 2, respectively. Increasing evidence is emerging in favor of a functional crosstalk between these two major KMT families. Critical Issues: Here, we review the current knowledge on the mechanisms of action and function of these enzymes, with particular emphasis on their interplay in the regulation of chromatin states and...

  17. Facioscapulohumeral Muscular Dystrophy As a Model for Epigenetic Regulation and Disease

    Himeda, Charis L.; Jones, Takako I.; Jones, Peter L.
    Significance: Aberrant epigenetic regulation is an integral aspect of many diseases and complex disorders. Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, is caused by disrupted genetic and epigenetic regulation of a macrosatellite repeat. FSHD provides a powerful model to investigate disease-relevant epigenetic modifiers and general mechanisms of epigenetic regulation that govern gene expression. Recent Advances: In the context of a genetically permissive allele, the one aspect of FSHD that is consistent across all known cases is the aberrant epigenetic state of the disease locus. In addition, certain mutations in the chromatin regulator SMCHD1 (structural...

  18. Autophagy Attenuates Noise-Induced Hearing Loss by Reducing Oxidative Stress

    Yuan, Hu; Wang, Xianren; Hill, Kayla; Chen, Jun; Lemasters, John; Yang, Shi-Ming; Sha, Su-Hua

  19. HJV and HFE Play Distinct Roles in Regulating Hepcidin

    Wu, Qian; Wang, Hao; An, Peng; Tao, Yunlong; Deng, Jiali; Zhang, Zhuzhen; Shen, Yuanyuan; Chen, Caiyong; Min, Junxia; Wang, Fudi

  20. Mitochondrial Protein Quality Control: The Mechanisms Guarding Mitochondrial Health

    Bohovych, Iryna; Chan, Sherine S.L.; Khalimonchuk, Oleh

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