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Antioxidants & Redox Signaling

Mahmoud-Sobhy Elkhwanky, Jukka Hakkola
SIGNIFICANCE: Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications, and adenosine diphosphate-ribosylation...
August 11, 2017: Antioxidants & Redox Signaling
Paola Fuschi, Biagina Maimone, Carlo Gaetano, Fabio Martelli
SIGNIFICANCE: Redox homeostasis plays a pivotal role in vascular cell function and its imbalance has a causal role in a variety of vascular diseases. Accordingly, the response of mammalian cells to redox cues requires precise transcriptional and post-transcriptional modulation of gene expression patterns. Recent Advances: Mounting evidence shows that nonprotein-coding RNAs (ncRNAs) are important for the functional regulation of most, if not all, cellular processes and tissues. Not surprisingly, a prominent role of ncRNAs has been identified also in the vascular system response to oxidative stress...
August 11, 2017: Antioxidants & Redox Signaling
Raul González, Francisco J Molina-Ruiz, Jose Antonio Barcena Ruiz, C Alicia Padilla, Jordi Muntané
SIGNIFICANCE: Nitric oxide (NO) is a physiopathological messenger generating different reactive nitrogen species (RNS) according to hypoxic, acidic and redox conditions. Recent Advances: RNS and reactive oxygen species (ROS) promote relevant post-translational modifications, such as nitrosation, nitration and oxidation, in critical components of cell proliferation and death, epithelial to mesenchymal transition and metastasis. CRITICAL ISSUES: The pro- or antitumoral properties of NO are dependent on local concentration, redox state, cellular status, duration of exposure and compartmentalization of NO generation...
August 10, 2017: Antioxidants & Redox Signaling
Xue Wu, Oana Tudoran, George Calin, Mircea Ivan
SIGNIFICANCE: The emerging connections between an increasing number of long noncoding RNAs (lncRNAs) and oncogenic hallmarks provide a new twist to tumor complexity. Recent Advances: In the present review, we highlight specific lncRNAs that have been studied in relationship to tumorigenesis, either as participants to the neoplastic process or as markers of pathway activity or drug response. These transcripts are typically deregulated by oncogenic or tumor-suppressing signals, or respond to microenvironmental conditions such as hypoxia...
August 10, 2017: Antioxidants & Redox Signaling
Amro Elgheznawy, Ingrid Fleming
SIGNIFICANCE: Platelets are anucleate blood cells involved in hemostasis and thrombosis. Although no longer able to generate RNA de novo, platelets contain mRNA, YRNA fragments and premature microRNAs (miRNAs) that inherit from megakaryocytes. Recent Advances. Novel sequencing techniques have helped identify the unexpectedly large number of RNA species present in platelets. Throughout their life time platelets can process the pre-existing pool of premature miRNA to give the fully functional miRNA that can regulated platelet protein expression and function...
August 10, 2017: Antioxidants & Redox Signaling
David D Roberts
Cells in multicellular organisms communicate extensively with neighboring cells and distant organs using a variety of secreted proteins and small molecules. Cells also reside in a structural extracellular matrix, and changes in its composition, mechanical properties, and post-translational modifications provide additional layers of communication. This Forum addresses emerging mechanisms by which redox signaling controls and is controlled by changes in the extracellular matrix, focusing on the roles of matricellular proteins...
August 10, 2017: Antioxidants & Redox Signaling
Michael John Kerins, Aikseng Ooi
SIGNIFICANCE: Iron and oxygen are intimately linked: iron is an essential nutrient utilized as a cofactor in enzymes for oxygen transport, oxidative phosphorylation, and metabolite oxidation. However, excess labile iron facilitates the formation of oxygen-derived free radicals capable of damaging biomolecules. Therefore, biological utilization of iron is a tightly regulated process. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor, which can respond to oxidative and electrophilic stress, regulates several genes involved in iron metabolism...
August 10, 2017: Antioxidants & Redox Signaling
Dina Vara, Joanna M Watt, Tiago M Fortunato, Harry Mellor, Matthew Burgess, Kate Wicks, Kimberly Mace, Shaun Reeksting, Anneke T Lubben, Caroline Pd Wheeler-Jones, Giordano Pula
AIMS: Deoxyribose-1-phosphate (dRP) is a pro-angiogenic paracrine stimulus released by cancer cells, platelets and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells. RESULTS: Live cell imaging, electron paramagnetic resonance (EPR), pull-down of dRP-interacting proteins followed by immunoblotting, gene silencing of different NOXs and their regulatory co-subunits by siRNA transfection, and experiments with inhibitors of the sugar transporter GLUT1 were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NADPH oxidase 2 (NOX2) complex, but not NOX4...
August 10, 2017: Antioxidants & Redox Signaling
Alessandro Matte, Luigia De Falco, Enrica Federti, Anna Cozzi, Achille Iolascon, Sonia Levi, Narla Mohandas, Alberto Zamo, Mariasole Bruno, Christophe Leboeuf, Anne Janin, Angela Siciliano, Thomas Ganz, Giorgia Federico, Francesca Carlomagno, Sebastian Mueller, Ines Silva, Carmine Carbone, Davide Melisi, D W Kim, Soo Young Choi, Lucia DE Franceschi
AIMS: Iron-overload (IO) is a life-threatening complication of chronic hemolytic disorders such as β-thalassemia. IO results in severe cellular oxidative damage, leading to organ failure. Peroxiredoxin-2 (Prx2), a typical 2-cysteine-(Cys)-peroxiredoxin, is an important component of cyto-protective system, but its response to IO is still to be fully defined. RESULTS: We studied the effects of IO on Prx2-knockout mice (Prx2-/-). The absence of Prx2 enhanced toxicity due to IO on erythropoiesis...
August 10, 2017: Antioxidants & Redox Signaling
Massimiliano Agostini, Gerry Melino, Francesca Bernassola
SIGNIFICANCE: The p53 family of transcription factors, including p53, p63 and p73, plays key roles in both biological and pathological processes, including cancer and neural development. Recent Advances: In recent years, a growing body of evidence has indicated that the entire p53 family is involved in the regulation of the central nervous system (CNS) functions as well as in the pathogenesis of several neurological disorders. Mechanistically, the p53 proteins control neuronal cell fate, terminal differentiation and survival, via a complex interplay amongst the family members...
August 10, 2017: Antioxidants & Redox Signaling
Bernd Zechmann
SIGNIFICANCE: Ascorbate is an essential antioxidant in plants. Total contents and its redox state in organelles are crucial to fight and signal oxidative stress. Recent Advances: With quantitative immunoelectron microscopy and biochemical methods, highest ascorbate contents have recently been measured in peroxisomes (23 mM) and the cytosol (22 mM), lowest ones in vacuoles (2 mM), and intermediate concentrations (4-16 mM) in all other organelles. CRITICAL ISSUES: The accumulation of ascorbate in chloroplasts and peroxisomes is crucial for plant defense...
August 10, 2017: Antioxidants & Redox Signaling
Nihay Laham-Karam, Pia Laitinen, Tiia A Turunen, Seppo Ylä-Herttuala
SIGNIFICANCE: The extent and breadth of transcription have recently been uncovered and this has revealed an extensive array of noncoding RNAs (ncRNAs). The biological role and significance of these ncRNAs have been realized and to date it appears that ncRNAs may have many important regulatory functions. ncRNAs are multifaceted and they induce a complexity of different types of transcriptional and posttranscriptional regulation, including gene activation. Recent Advances: Association of ncRNAs with gene activation is an important finding...
August 10, 2017: Antioxidants & Redox Signaling
Britta Kunkemoeller, Themis R Kyriakides
SIGNIFICANCE: Impaired wound healing is a major complication of diabetes, and can lead to development of chronic foot ulcers in a significant number of patients. Despite the danger posed by poor healing, very few specific therapies exist, leaving patients at risk of hospitalization, amputation, and further decline in overall health. Recent Advances: Redox signaling is a key regulator of wound healing, especially through its influence on the extracellular matrix (ECM). Normal redox signaling is disrupted in diabetes leading to several pathological mechanisms that alter the balance between reactive oxygen species (ROS) generation and scavenging...
August 10, 2017: Antioxidants & Redox Signaling
Huocong Huang, Wenting Du, Rolf A Brekken
SIGNIFICANCE: The extracellular matrix (ECM) is the non-cellular component secreted by cells and present within all tissues and organs. The ECM provides the structural support required for tissue integrity and also contributes to diseases, including cancer. Many diseases rich in ECM are characterized by changes in reactive oxygen species (ROS) levels that have been shown to have important context-dependent functions. Recent Advances: Many studies have found that the ECM affects ROS production through integrins...
August 9, 2017: Antioxidants & Redox Signaling
Agnès Delaunay-Moisan, Alise Ponsero, Michel Toledano
SIGNIFICANCE: Disturbance of glutathione metabolism is a hallmark of numerous diseases, yet glutathione functions are poorly understood. One key to this question is to consider its functional compartmentation. In the endoplasmic reticulum (ER), protein folding involves disulfide bond formation catalyzed by the thiol oxidase Ero1 and proteins from the disulfide isomerase family (PDI). GSH competes with substrates for oxidation by Ero1, but its requirement for ER oxidative protein folding is questioned...
August 9, 2017: Antioxidants & Redox Signaling
Bridgette M Cumming, Krishna C Chinta, Vineel P Reddy, Adrie Jc Steyn
SIGNIFICANCE: L-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria and some fungi. In contrast to other low molecular weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological pH, which makes it resistant to autoxidation. Ergothioneine regulates microbial physiology and enables survival of the microbes under stressful conditions encountered in their natural environments. In particular, ergothioneine enables pathogenic microbes, such as Mycobacterium tuberculosis (Mtb), to withstand hostile environments within the host to establish infection...
August 9, 2017: Antioxidants & Redox Signaling
Orazio Cantoni, Andrea Guidarelli, Mara Fiorani
SIGNIFICANCE: The mitochondrial fraction of l-ascorbic acid (AA) is of critical importance for the regulation of the redox status of these organelles and for cell survival. Recent Advances: Most cell types take up AA by the high-affinity sodium-dependent vitamin C transporter 2 (SVCT2) sensitive to inhibition by dehydroascorbic acid (DHA). DHA can also be taken up by glucose transporters (GLUTs) and then reduced back to AA. DHA concentrations, normally very low in biological fluids, may only become significant next to superoxide-releasing cells...
August 9, 2017: Antioxidants & Redox Signaling
Yuzheng Zhao, Zhuo Zhang, Yejun Zou, Yi Yang
SIGNIFICANCE: Beyond their roles as redox currency in living organisms, pyridine dinucleotides (NAD(+)/NADH and NADP(+)/NADPH) are also precursors or cosubstrates of great significance in various physiologic and pathologic processes. Recent Advances: For many years, it was challenging to develop methodologies for monitoring pyridine dinucleotides in situ or in vivo. Recent advances in fluorescent protein-based sensors provide a rapid, sensitive, specific, and real-time readout of pyridine dinucleotide dynamics in single cells or in vivo, thereby opening a new era of pyridine dinucleotide bioimaging...
August 9, 2017: Antioxidants & Redox Signaling
Helmut Sies, Ludwig E Feinendegen
Hydrogen peroxide (H2O2) is a stable product of water radiolysis, occurring at nanomolar concentration upon low-dose ionizing radiation (LDIR) (<100 mGy). In view of the recent recognition of H2O2 as a central redox signaling molecule that, likewise, is maintained in the nanomolar range in cells, we propose a role for H2O2 in radiation hormesis. LDIR is capable of utilizing known molecular redox master switches such as Nrf2/Keap1 or NF-κB/IκB to effect adaptive resistance. This leads to the hypothesis that, as a normal component of the exposome, LDIR mediates hormetic effects by H2O2 signaling...
August 7, 2017: Antioxidants & Redox Signaling
Nathalie Khoury, Kevin B Koronowski, Juan I Young, Miguel A Perez-Pinzon
Sirtuins are an evolutionarily conserved family of NAD(+)-dependent lysine deacylases and ADP ribosylases. Their requirement for NAD(+) as a cosubstrate allows them to act as metabolic sensors that couple changes in the energy status of the cell to changes in cellular physiological processes. NAD(+) levels are affected by several NAD(+)-producing and NAD(+)-consuming pathways as well as by cellular respiration. Thus their intracellular levels are highly dynamic and are misregulated in a spectrum of metabolic disorders including cerebral ischemia...
August 7, 2017: Antioxidants & Redox Signaling
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