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Free Radical Biology & Medicine

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https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#1
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908784/cisplatin-induced-mitochondrial-dysfunction-is-associated-with-impaired-cognitive-function-in-rats
#2
Naomi Lomeli, Kaijun Di, Jennifer Czerniawski, John F Guzowski, Daniela A Bota
PURPOSE: Chemotherapy-related cognitive impairment (CRCI) is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems. No effective treatments for CRCI are currently available. Here we examined the mechanisms involving cisplatin-induced hippocampal damage following cisplatin administration in a rat model and in cultured rat hippocampal neurons and neural stem/progenitor cells (NSC). We also assessed the protective effects of the antioxidant, N-acetylcysteine in mitigating these damages...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908783/lipid-peroxidation-in-face-of-dna-damage-dna-repair-and-other-cellular-processes
#3
Barbara Tudek, Daria Zdżalik-Bielecka, Agnieszka Tudek, Konrad Kosicki, Anna Fabisiewicz, Elżbieta Speina
Exocyclic adducts to DNA bases are formed as a consequence of exposure to certain environmental carcinogens as well as inflammation and lipid peroxidation (LPO). Complex family of LPO products gives rise to a variety of DNA adducts, which can be grouped in two classes: (i) small etheno-type adducts of strong mutagenic potential, and (ii) bulky, propano-type adducts, which block replication and transcription, and are lethal lesions. Etheno-DNA adducts are removed from the DNA by base excision repair (BER), AlkB and nucleotide incision repair enzymes (NIR), while substituted propano-type lesions by nucleotide excision repair (NER) and homologous recombination (HR)...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#4
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27908781/heme-oxygenase-1-metabolite-biliverdin-not-iron-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication
#5
Angke Zhang, Hong Duan, Na Li, Lijuan Zhao, Fengxing Pu, Baicheng Huang, Chunyan Wu, Yuchen Nan, Taofeng Du, Yang Mu, Qin Zhao, Yani Sun, Gaiping Zhang, Julian A Hiscox, En-Min Zhou, Shuqi Xiao
Porcinereproductiveandrespiratorysyndromevirus (PRRSV) causes significant economic losses to the pork industry worldwide. Previously, we demonstrated that heme oxygenase-1 (HO-1) interferes with PRRSV replication. To elucidate the mechanisms involved, here we assess whether the HO-1 downstream metabolites biliverdin (BV) and/or iron mediate the HO-1 antiviral effect. We demonstrate a BV concentration-dependent suppression of PRRSV replication and show that virions are not directly inactivated by BV. Additionally, BV or N-acetyl cysteine (NAC) significantly reduced reactive oxygen species (ROS) in PRRSV-infected MARC-145 cells; however, because NAC did not reduce viral load, the BV antiviral effect is independent of decreased ROS levels...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27903453/repair-of-8-oxo-7-8-dihydroguanine-in-prokaryotic-and-eukaryotic-cells-properties-and-biological-roles-of-the-fpg-and-ogg1-dna-n-glycosylases
#6
Serge Boiteux, Franck Coste, Bertrand Castaing
Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases...
November 26, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27894771/radiation-induced-dna-protein-cross-links-mechanisms-and-biological-significance
#7
Toshiaki Nakano, Xu Xu, Amir M H Salem, Mahmoud I Shoulkamy, Hiroshi Ide
Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors...
November 25, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890643/coordination-of-dna-single-strand-break-repair
#8
Rachel Abbotts, David M Wilson
The genetic material of all organisms is susceptible to modification. In some instances, these changes are programmed, such as the formation of DNA double strand breaks during meiotic recombination to generate gamete variety or class switch recombination to create antibody diversity. However, in most cases, genomic damage is potentially harmful to the health of the organism, contributing to disease and aging by promoting deleterious cellular outcomes. A proportion of DNA modifications are caused by exogenous agents, both physical (namely ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene, alkylating agents, platinum compounds and psoralens), which can produce numerous forms of DNA damage, including a range of "simple" and helix-distorting base lesions, abasic sites, crosslinks and various types of phosphodiester strand breaks...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890642/protective-effect-of-quercetin-on-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-in-mice-is-mediated-by-modulating-intestinal-microbiota-imbalance-and-related-gut-liver-axis-activation
#9
David Porras, Esther Nistal, Susana Martínez-Flórez, Sandra Pisonero-Vaquero, José Luis Olcoz, Ramiro Jover, Javier González-Gallego, María Victoria García-Mediavilla, Sonia Sánchez-Campos
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890641/specific-point-mutations-in-key-redox-enzymes-are-associated-with-chemoresistance-in-epithelial-ovarian-cancer
#10
Nicole M Fletcher, Jimmy Belotte, Mohammed G Saed, Ira Memaj, Michael P Diamond, Robert T Morris, Ghassan M Saed
Oxidative stress plays an important role in the pathophysiology of ovarian cancer. Resistance to chemotherapy presents a significant challenge for ovarian cancer treatment. Specific single nucleotide polymorphisms (SNPs) in key redox enzymes have been associated with ovarian cancer survival and progression. The objective of this study was to determine whether chemotherapy induces point mutations in key redox enzymes that lead to the acquisition of chemoresistance in epithelial ovarian cancer (EOC). Human EOC cell lines and their chemoresistant counterpart were utilized for this study...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890640/an-mtdna-mutation-accelerates-liver-aging-by-interfering-with-the-ros-response-and-mitochondrial-life-cycle
#11
Jan Niemann, Cindy Johne, Susanne Schröder, Franziska Koch, Saleh M Ibrahim, Julia Schultz, Markus Tiedge, Simone Baltrusch
Mitochondrial dysfunction affects liver metabolism, but it remains unclear whether this interferes with normal liver aging. We investigated several mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse strain compared with the control C57BL/6NTac strain over 18 months of life. The C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac-mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen species (ROS) production to C57BL/6NTac mice...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890639/oxidized-c5-methyl-cytosine-bases-in-dna-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxycytosine
#12
Arne Klungland, Adam B Robertson
Recent reports suggest that the Tet enzyme family catalytically oxidize 5-methylcytosine in mammalian cells. The oxidation of 5-methylcytosine can result in three chemically distinct species - 5-hydroxymethylcytsine, 5-formylcytosine, and 5-carboxycytosine. While the base excision repair machinery processes 5-formylcytosine and 5-carboxycytosine rapidly, 5-hydroxymethylcytosine is stable under physiological conditions. As a stable modification 5-hydroxymethylcytosine has a broad range of functions, from stem cell pluriopotency to tumorigenesis...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890638/aberrant-base-excision-repair-pathway-of-oxidatively-damaged-dna-implications-for-degenerative-diseases
#13
Ibtissam Talhaoui, Bakhyt T Matkarimov, Thierry Tchenio, Dmitry O Zharkov, Murat K Saparbaev
In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890722/diabetes-induced-hepatic-oxidative-stress-a-new-pathogenic-role-for-glycated-albumin
#14
Jessica Patche, Dorothée Girard, Aurélie Catan, Florence Boyer, Anthony Dobi, Cynthia Planesse, Nicolas Diotel, Alexis Guerin-Dubourg, Pascal Baret, Susana B Bravo, Beatriz Paradela-Dobarro, Ezequiel Álvarez, M Faadiel Essop, Olivier Meilhac, Emmanuel Bourdon, Philippe Rondeau
Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively...
November 23, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890721/reactive-gamma-ketoaldehydes-as-novel-activators-of-hepatic-stellate-cells-in-vitro
#15
Lisa Longato, Fausto Andreola, Sean S Davies, Jackson L Roberts, Giuseppe Fusai, Massimo Pinzani, Kevin Moore, Krista Rombouts
AIMS: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype. Isolevuglandins (IsoLG) are a family of acyclic γ-ketoaldehydes formed through oxidation of arachidonic acid or as by-products of the cyclooxygenase pathway. IsoLGs are highly reactive aldehydes which are efficient at forming protein adducts and cross-links at concentrations 100-fold lower than 4-hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG could induce activation of HSC...
November 23, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27888001/antioxidants-and-hne-in-redox-homeostasis
#16
REVIEW
Wojciech Łuczaj, Agnieszka Gęgotek, Elżbieta Skrzydlewska
Under physiological conditions, cells are in a stable state known as redox homeostasis, which is maintained by the balance between continuous ROS/RNS generation and several mechanisms involved in antioxidant activity. ROS overproduction results in alterations in the redox homeostasis that promote oxidative damage to major components of the cell, including the biomembrane phospholipids. Lipid peroxidation subsequently generates a diverse set of products, including α,β-unsaturated aldehydes. Of these products, 4-hydroxy-2-nonenal (HNE) is the most studied aldehyde on the basis of its involvement in cellular physiology and pathology...
November 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27884704/enhanced-aggressiveness-of-bystander-cells-in-an-anti-tumor-photodynamic-therapy-model-role-of-nitric-oxide-produced-by-targeted-cells
#17
Jerzy Bazak, Jonathan M Fahey, Katarzyna Wawak, Witold Korytowski, Albert W Girotti
The bystander effects of anti-cancer ionizing radiation have been widely studied, but far less is known about such effects in the case of non-ionizing photodynamic therapy (PDT). In the present study, we tested the hypothesis that photodynamically-stressed prostate cancer PC3 cells can elicit nitric oxide (NO)-mediated pro-growth/migration responses in non-stressed bystander cells. A novel approach was used whereby both cell populations existed on a culture dish, but made no physical contact with one other...
November 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27884703/mechanistic-and-biological-considerations-of-oxidatively-damaged-dna-for-helicase-dependent-pathways-of-nucleic-acid-metabolism
#18
Jack D Crouch, Robert M Brosh
Cells are under constant assault from reactive oxygen species that occur endogenously or arise from environmental agents. An important consequence of such stress is the generation of oxidatively damaged DNA, which is represented by a wide range of non-helix distorting and helix-distorting bulkier lesions that potentially affect a number of pathways including replication and transcription; consequently DNA damage tolerance and repair pathways are elicited to help cells cope with the lesions. The cellular consequences and metabolism of oxidatively damaged DNA can be quite complex with a number of DNA metabolic proteins and pathways involved...
November 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27880870/formation-and-processing-of-dna-damage-substrates-for-the-hneil-enzymes
#19
Aaron M Fleming, Cynthia J Burrows
Reactive oxygen species (ROS) are harnessed by the cell for signaling at the same time as being detrimental to cellular components such as DNA. The genome and transcriptome contain instructions that can alter cellular processes when oxidized. The guanine (G) heterocycle in the nucleotide pool, DNA, or RNA is the base most prone to oxidation. The oxidatively-derived products of G consistently observed in high yields from hydroxyl radical, carbonate radical, or singlet oxygen oxidations under conditions modeling the cellular reducing environment are discussed...
November 20, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27880869/the-impact-of-metagenomic-interplay-on-the-mosquito-redox-homeostasis
#20
REVIEW
Cody J Champion, Jiannong Xu
Mosquitoes are exposed to oxidative challenges throughout their life cycle. The primary challenge comes from a blood meal. The blood digestion turns the midgut into an oxidative environment, which imposes pressure not only on mosquito fecundity and other physiological traits but also on the microbiota in the midgut. During evolution, mosquitoes have developed numerous oxidative defense mechanisms to maintain redox homeostasis in the midgut. In addition to antioxidants, SOD, catalase, and glutathione system, sufficient supply of the reducing agent, NADPH, is vital for a successful defense against oxidative stress...
November 20, 2016: Free Radical Biology & Medicine
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