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Free Radical Biology & Medicine

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https://www.readbyqxmd.com/read/28438660/reaction-of-hypotaurine-or-taurine-with-superoxide-produces-the-organic-peroxysulfonic-acid-peroxytaurine
#1
Roxanna Q Grove, Steven J Karpowicz
Hypotaurine and taurine are amino acid derivatives and abundant molecules in many eukaryotes. The biological reaction in which hypotaurine is converted to taurine remains poorly understood. Here, hypotaurine and taurine were observed to react with superoxide anion in vitro to form the novel molecule peroxytaurine. In contrast, hypotaurine reacts with hydrogen peroxide to form taurine, but taurine does not react with hydrogen peroxide in vitro. Mass and NMR spectrometry as well as FTIR and Raman spectroscopy support the molecular characterization of peroxytaurine...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28438659/the-nrf2-activator-dh404-attenuates-adverse-ventricular-remodelling-post-myocardial-infarction-by-modifying-redox-signalling
#2
Kristen J Bubb, Cindy Kok, Owen Tang, Nathalie B Rasko, Asa Birna Birgisdottir, Thomas Hansen, Rebecca Ritchie, Ravinay Bhindi, Scott A Reisman, Colin Meyer, Keith Ward, Keyvan Karimi Galougahi, Gemma A Figtree
BACKGROUND: The novel synthetic triterpenoid, bardoxolone methyl, has the ability to upregulate cytoprotective proteins via induction of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising therapeutic agent in disease states characterized by dysregulated oxidative signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO-trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct cardiac remodeling in rats. METHODS/RESULTS: DH404, administered from day 2 post myocardial infarction (MI: 30 min transient ischemia followed by reperfusion) resulted in almost complete protection against adverse ventricular remodeling as assessed at day 28 (left ventricular end-systolic area: sham 0...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28438658/antioxidants-reduce-neurodegeneration-and-accumulation-of-pathologic-tau-proteins-in-the-auditory-system-after-blast-exposure
#3
Xiaoping Du, Matthew B West, Qunfeng Cai, Weihua Cheng, Donald L Ewert, Wei Li, Robert A Floyd, Richard D Kopke
Cochlear neurodegeneration commonly accompanies hair cell loss resulting from aging, ototoxicity, or exposures to intense noise or blast overpressures. However, the precise pathophysiological mechanisms that drive this degenerative response have not been fully elucidated. Our laboratory previously demonstrated that non-transgenic rats exposed to blast overpressures exhibited marked somatic accumulation of neurotoxic variants of the microtubule-associated protein, Tau, in the hippocampus. In the present study, we extended these analyses to examine neurodegeneration and pathologic Tau accumulation in the auditory system in response to blast exposure and evaluated the potential therapeutic efficacy of antioxidants on short-circuiting this pathological process...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28438657/the-thiol-of-human-serum-albumin-acidity-microenvironment-and-mechanistic-insights-on-its-oxidation-to-sulfenic-acid
#4
Jenner Bonanata, Lucía Turell, Laura Antmann, Gerardo Ferrer-Sueta, Santiago Botasini, Eduardo Méndez, Beatriz Alvarez, E Laura Coitiño
Human serum albumin (HSA) has a single reduced cysteine residue, Cys34, whose acidity has been controversial. Three experimental approaches (pH-dependence of reactivity towards hydrogen peroxide, ultraviolet titration and infrared spectroscopy) are used to determine that the pKa value in delipidated HSA is 8.1 ± 0.2 at 37°C and 0.1M ionic strength. Molecular dynamics simulations of HSA in the sub-microsecond timescale show that while sulfur exposure to solvent is limited and fluctuating in the thiol form, it increases in the thiolate, stabilized by a persistent hydrogen-bond (HB) network involving Tyr84 and bridging waters to Asp38 and Gln33 backbone...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28435052/neurovascular-neuroenergetic-coupling-axis-in-the-brain-master-regulation-by-nitric-oxide-and-consequences-in-aging-and-neurodegeneration
#5
REVIEW
Cátia F Lourenço, Ana Ledo, Rui M Barbosa, João Laranjinha
The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O2 and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28435051/akt1-nf%C3%AE%C2%BAb-signaling-pathway-activation-by-a-small-molecule-dma-confers-radioprotection-to-intestinal-epithelium-in-xenograft-model
#6
Vinod Tiwari, Mohammad Zahid Kamran, Atul Ranjan, Hemlata Nimesh, Manish Singh, Vibha Tandon
Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28435050/the-human-krebs-cycle-2-oxoglutarate-dehydrogenase-complex-creates-an-additional-source-of-superoxide-hydrogen-peroxide-from-2-oxoadipate-as-alternative-substrate
#7
Natalia S Nemeria, Gary Gerfen, Elena Guevara, Pradeep Reddy Nareddy, Michal Szostak, Frank Jordan
Recently, we reported that the human 2-oxoglutarate dehydrogenase (hE1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHc) could produce the reactive oxygen species superoxide and hydrogen peroxide (detected by chemical means) from its substrate 2-oxoglutarate (OG), most likely concurrently with one-electron oxidation by dioxygen of the thiamin diphosphate (ThDP)-derived enamine intermediate to a C2α-centered radical (detected by Electron Paramagnetic Resonance) [Nemeria et al., 2014; Ambrus et al...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#8
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433661/differential-protein-acetylation-assists-import-of-excess-sod2-into-mitochondria-and-mediates-sod2-aggregation-associated-with-cardiac-hypertrophy-in-the-murine-sod2-tg-heart
#9
Liwen Zhang, Chwen-Lih Chen, Patrick T Kang, Zhicheng Jin, Yeong-Renn Chen
SOD2 is the primary antioxidant enzyme neutralizing ((•))O2((-)) in mitochondria. Cardiac-specific SOD2 overexpression (SOD2-tg) induces supernormal function and cardiac hypertrophy in the mouse heart. However, the reductive stress imposed by SOD2 overexpression results in protein aggregation of SOD2 pentamers and differential hyperacetylation of SOD2 in the mitochondria and cytosol. Here, we studied SOD2 acetylation in SOD2-tg and wild-type mouse hearts. LC-MS/MS analysis indicated the presence of four acetylated lysines in matrix SOD2 and nine acetylated lysines in cytosolic SOD2 from the SOD2-tg heart...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433660/redox-regulation-of-gasotransmission-in-the-vascular-system-a-focus-on-angiogenesis
#10
REVIEW
Rajesh K Mistry, Alison C Brewer
Reactive oxygen species have emerged as key participants in a broad range of physiological and pathophysiological processes, not least within the vascular system. Diverse cellular functions which have been attributed to some of these pro-oxidants within the vasculature include the regulation of blood pressure, neovascularisation and vascular inflammation. We here highlight the emerging roles of the enzymatically-generated reaction oxygen species, O2(-) and H2O2, in the regulation of the functions of the gaseous signalling molecules: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H2S)...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431962/structural-basis-chemical-driving-forces-and-biological-implications-of-flavones-as-cu-ii-ionophores
#11
Fang Dai, Wen-Jing Yan, Yu-Ting Du, Xia-Zhen Bao, Xiu-Zhuang Li, Bo Zhou
A main biochemical property of cancer cells, compared with normal cells, is altered redox status including increased levels of copper to maintain their malignant phenotypes. Thus, increasing copper accumulation, by using ionophores, to disrupt abnormal redox homeostasis of cancer cells may be an important anticancer strategy. Naturally occurring molecules with extraordinarily diverse chemical scaffolds are an important source of inspiration for developing copper ionophores. Dietary flavonoids are well-characterized copper chelators and show cancer chemopreventive potential, but their ionophoric role for redox-active copper and the related biological implications have remained unknown...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#12
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28428001/cholesterol-and-related-sterols-autoxidation
#13
REVIEW
Chiara Zerbinati, Luigi Iuliano
Cholesterol is a unique lipid molecule providing the building block for membranes, hormone, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the iso-octyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28428000/selected-oxidative-stress-biomarkers-in-antenatal-diagnosis-as-11-14-gestational-weeks
#14
Marek Pietryga, Piotr Dydowicz, Kinga Toboła, Marta Napierała, Izabela Miechowicz, Anna Gąsiorowska, Maciej Brązert, Ewa Florek
The primary objective in modern obstetrics and prenatal diagnosis is to predict risks of congenital abnormalities. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the risk of foetal chromosomal aberration evaluated at the first trimester screening. A series of studies show that balanced free radical activity and oxidative homeostasis are essential for proper bodily growth and function. Reactive oxygen species (ROS) may be one of the factors associated with disruption of cell cycle and tissue development, thus leading to developmental abnormalities...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427999/serpinb1-ameliorates-acute-lung-injury-in-liver-transplantation-through-erk1-2-mediated-stat3-dependent-ho-1-induction
#15
Weifeng Yao, Haobo Li, Gangjian Luo, Xiang Li, Chaojin Chen, Dongdong Yuan, Xinjin Chi, Zhengyuan Xia, Ziqing Hei
BACKGROUND: Postoperative acute lung injury(ALI) is a severe complication after liver transplantation, which severely affects postoperative patients' survival. The underlying mechanism is largely unknown and effective treatment limited. We explored the role of serpin protease inhibitor B1(SERPINB1), a potent inhibitor of neutrophil serine proteases, in ALI in liver transplantation and its interplay with signal transducer and activator of transcription 3(STAT3) and heme oxygenase-1(HO-1)...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427998/nitric-oxide-regulated-proteolysis-of-human-cyp2b6-via-the-ubiquitin-proteasome-system
#16
Choon-Myung Lee, Shweta Tripathi, Edward T Morgan
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28419867/sustained-blockade-of-ascorbic-acid-transport-associated-with-marked-svct1-loss-in-rat-hepatocytes-containing-increased-ascorbic-acid-levels-after-partial-hepatectomy
#17
Mafalda Maldonado, Eveling Inostroza, Eduardo Peña, Natacha Moncada, Lorena Mardones, José Luis Medina, Alejandra Muñoz, Marcell Gatica, Marcelo Villagrán, Elizabeth Escobar, Pamela Mendoza, Francisco J Roa, Mauricio González, Paula Guzmán, Francisco A Gutiérrez-Castro, Karen Sweet, Carola Muñoz-Montesino, Juan Carlos Vera, Coralia I Rivas
The liver has an extraordinary regenerative capacity in response to partial hepatectomy (PHx), which develops with neither tissue inflammation response nor alterations in the whole organism. This process is highly coordinated and it has been associated with changes in glutathione (GSH) metabolism. However, there are no reports indicating ascorbic acid (AA) levels after partial hepatectomy. AA and GSH act integrally as an antioxidant system that protects cells and tissues from oxidative damage and imbalance observed in a variety of diseases that affect the liver...
April 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28419866/o-aminobenzoyl-s-nitrosoglutathione-a-fluorogenic-cell-permeable-pseudo-substrate-for-s-nitrosoglutathione-reductase
#18
Bei Lei Sun, Lisa Palmer, Shagufta Rehman Alam, Itunuoluwa Adekoya, Kathleen Brown-Steinke, Ammasi Periasamy, Bulent Mutus
S-nitrosoglutathione reductase (GSNOR) is a multifunctional enzyme. It can catalyze NADH-dependent reduction of S-nitrosoglutathione (GSNO); as well as NAD(+)-dependent oxidation of hydroxymethylglutathione (HMGSH; an adduct formed by the spontaneous reaction between formaldehyde and glutathione). While initially recognized as the enzyme that is involved in formaldehyde detoxification, increasing amount of evidence has shown that GSNOR also plays a significant role in nitric oxide mediated signaling through its modulation of protein S-nitrosothiol signaling...
April 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28419865/the-nitroxyl-donor-angeli-s-salt-ameliorates-staphylococcus-aureus-induced-septic-arthritis-in-mice
#19
Larissa Staurengo-Ferrari, Kenji W Ruiz-Miyazawa, Felipe A Pinho-Ribeiro, Talita P Domiciano, Victor Fattori, Sandra S Mizokami, Jacinta S Pelayo, Juliano Bordignon, Florêncio Figueiredo, Rubia Casagrande, Katrina M Miranda, Waldiceu A Verri
Septic arthritis is a severe and rapidly debilitating disease associated with severe joint pain, inflammation and oxidative stress. Nitroxyl (HNO) has become a nitrogen oxide of significant interest due to its pharmacological endpoints that are potentially favorable for treating varied diseases. However, whether HNO also serves as a treatment to septic arthritis is currently unknown. The aim of this study was to investigate the effect of the HNO donor, Angeli's salt (AS), in the outcome of chronic Staphylococcus aureus (S...
April 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28416347/blood-collection-vials-and-clinically-used-intravenous-fluids-contain-significant-amounts-of-nitrite
#20
Luis E F Almeida, Sayuri Kamimura, Margaret Y Nettleton, Celia M de Souza Batista, Elizabeth Walek, Alfia Khaibullina, Li Wang, Zenaide M N Quezado
The biology of the inorganic anion nitrite is linked to nitric oxide (NO) as nitrite can be reduced to NO and mediate its biological activities. Thus, studies of nitrite biology require sensitive and selective chemical assays. The acetic and ascorbic acids method is selective for nitrite and measures it in biological matrices. However, one of the pitfalls of nitrite measurements is its ubiquitous presence in sample collection tubes. Here, we showed high levels of nitrite in collection tubes containing EDTA, sodium citrate or sodium heparin and smaller amounts in tubes containing lithium heparin or serum clot activator...
April 14, 2017: Free Radical Biology & Medicine
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