Frailty as a phenotypic manifestation of underlying oxidative stress.
ntilde;as L Abstract Oxidative stress plays a key role in the aging process. Lifestyle behaviours including low physical activity and inadequate nutritional habits in addition to genetic susceptibility and some chronic diseases compromise physiological response to free radicals and promote oxidative damage. Reduced resilience (referred to the ability to respond to stressors or adverse conditions) or functional reserve in isolated organs or systems determines clinical manifestations as the age-related chronic diseases while multisystemic dysfunction results in the frailty phenotype. In older adults, frailty, but no...
Source: Free Radical Biology and Medicine - August 15, 2019 Category: Biology Authors: El Assar M, Angulo J, Rodríguez-Mañas L Tags: Free Radic Biol Med Source Type: research

Sulforaphane protects from myocardial ischemia-reperfusion damage through the balanced activation of Nrf2/AhR.
In this study we compared the effectiveness between sulforaphane (SFN) and the mechanical maneuver of post-conditioning (PostC) to confer cardioprotection in an in vivo cardiac ischemia-reperfusion model. We also evaluated if additional mechanisms, besides Nrf2 activation, contributed to cardioprotection. Our results showed that SFN induced an enhanced protective response compared to PostC, although both preserved cardiac function, decreased infarct size, oxidative stress and inflammation. Both strategies shared common protective pathways; however, in the protection conferred by SFN, Nrf2 activation was demonstrated, along...
Source: Free Radical Biology and Medicine - August 15, 2019 Category: Biology Authors: Silva-Palacios A, Ostolga-Chavarría M, Sánchez-Garibay C, Rojas-Morales P, Galván-Arzate S, Buelna-Chontal M, N P, Pedraza-Chaverrí J, M K, C Z Tags: Free Radic Biol Med Source Type: research

Redox regulation of hepatic NLRP3 inflammasome activation and immune dysregulation in trichloroethene-mediated autoimmunity.
Abstract Trichloroethene (TCE) exposure is associated with the development of various autoimmune diseases (ADs), including autoimmune hepatitis (AIH) and systemic lupus erythematosus (SLE), potentially through the generation of excessive reactive oxygen and nitrogen species (RONS; oxidative stress). However, the mechanisms by which oxidative stress contributes to these TCE-mediated ADs are not fully understood, and are the focus of current investigation. Female MRL+/+ mice were treated with TCE along with or without antioxidant N-acetylcysteine (NAC) for 6 weeks (TCE, 10 mmol/kg, i. p., every 4th day; NAC, 25...
Source: Free Radical Biology and Medicine - August 13, 2019 Category: Biology Authors: Wang H, Wang G, Liang Y, Du X, Boor PJ, Sun J, Khan MF Tags: Free Radic Biol Med Source Type: research

Protective effect of dihydroartemisinin in inhibiting senescence of myeloid-derived suppressor cells from lupus mice via Nrf2/HO-1 pathway.
In conclusion, MDSCs senescence played a vital role in the pathogenesis of SLE, and DHA attenuated the symptoms of SLE via relieving MDSCs aging involved in the induction of Nrf2/HO-1 pathway. PMID: 31419476 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - August 13, 2019 Category: Biology Authors: Li D, Qi J, Wang J, Pan Y, Li J, Xia X, Dou H, Hou Y Tags: Free Radic Biol Med Source Type: research

Opposing action of NCoR1 and PGC-1 α in mitochondrial redox homeostasis.
Opposing action of NCoR1 and PGC-1α in mitochondrial redox homeostasis. Free Radic Biol Med. 2019 Aug 10;: Authors: Lima TI, Guimarães DSPSF, Oliveira AG, Araujo H, Sponton CHG, Pinto NS, Saito A, Figueira ACM, Palameta S, Bajgelman MC, Calixto A, Pinto S, Mori MA, Orofino J, Perissi V, Mottis A, Auwerx J, Silveira LR Abstract The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encoding for ant...
Source: Free Radical Biology and Medicine - August 10, 2019 Category: Biology Authors: Lima TI, Guimarães DSPSF, Oliveira AG, Araujo H, Sponton CHG, Pinto NS, Saito A, Figueira ACM, Palameta S, Bajgelman MC, Calixto A, Pinto S, Mori MA, Orofino J, Perissi V, Mottis A, Auwerx J, Silveira LR Tags: Free Radic Biol Med Source Type: research

Oxidized base 8-oxoguanine, a product of DNA repair processes, contributes to dendritic cell activation.
, Boldogh I, Bácsi A Abstract A growing body of evidence suggests that elevated levels of reactive oxygen species (ROS) in the airways caused by exposure to gas phase pollutants or particulate matter are able to activate dendritic cells (DCs); however, the exact mechanisms are still unclear. When present in excess, ROS can modify macromolecules including DNA. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base excision repair (BER) pathway. Studies have also demonstrated that in addition to its role in ...
Source: Free Radical Biology and Medicine - August 10, 2019 Category: Biology Authors: Pázmándi K, Sütő M, Fekete T, Varga A, Boldizsár E, Boldogh I, Bácsi A Tags: Free Radic Biol Med Source Type: research

Free heme regulates placenta growth factor through NRF2-antioxidant response signaling.
Abstract Free heme activates erythroblasts to express and secrete Placenta Growth Factor (PlGF), an angiogenic peptide of the VEGF family. High circulating levels of PlGF have been associated in experimental animals and in patients with sickle cell disease with echocardiographic markers of pulmonary hypertension, a life-limiting complication associated with more intense hemolysis. We now show that the mechanism of heme regulation of PlGF requires the contribution of the key antioxidant response regulator NRF2. Mimicking the effect of heme, the NRF2 agonist sulforaphane stimulates the PlGF transcript level nearly 3...
Source: Free Radical Biology and Medicine - August 10, 2019 Category: Biology Authors: Kapetanaki MG, Gbotosho OT, Sharma D, Weidert F, Ofori-Acquah SF, Kato GJ Tags: Free Radic Biol Med Source Type: research

Pyruvate kinase M2: A simple molecule with complex functions.
Abstract Pyruvate kinase M2 is a critical enzyme that regulates cell metabolism and growth under different physiological conditions. In its metabolic role, pyruvate kinase M2 catalyzes the last glycolytic step which converts phosphoenolpyruvate to pyruvate with the generation of ATP. Beyond this metabolic role in glycolysis, PKM2 regulates gene expression in the nucleus, phosphorylates several essential proteins that regulate major cell signaling pathways, and contribute to the redox homeostasis of cancer cells. The expression of PKM2 has been demonstrated to be significantly elevated in several types of cancer, a...
Source: Free Radical Biology and Medicine - August 8, 2019 Category: Biology Authors: Alquraishi M, Puckett DL, Alani DS, Humidat AS, Frankel VD, Donohoe DR, Whelan J, Bettaieb A Tags: Free Radic Biol Med Source Type: research

Profiles of brain oxidative damage, ventricular alterations, and neurochemical metabolites in the striatum of PINK1 knockout rats as functions of age and gender: Relevance to Parkinson disease.
Abstract Parkinson disease (PD) is the second most common neurodegenerative disease associated with aging. Dopaminergic neuronal degeneration and α-synuclein aggregation are commonly found in PD brain. Oxidative damage and inflammation often are considered as etiological factors of PD, although the detailed mechanisms still remain unknown. Gender and aging are two important risk factors to PD, and gene mutations and certain environmental factors have been implicated in this disease. The current study employed PTEN-induced putative kinase -1 (PINK1) knockout (KO) rats, since mutations in PINK-1 lead to famili...
Source: Free Radical Biology and Medicine - August 8, 2019 Category: Biology Authors: Ren X, Hinchie A, Swomley A, Powell DK, Butterfield DA Tags: Free Radic Biol Med Source Type: research

Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis.
Abstract Postovulatory aging is known to compromise the oocyte quality as well as subsequent embryo development in many different animal models, and becomes one of the most intractable issues that limit the outcome of human assisted reproductive technology (ART). However, the strategies to prevent the deterioration of aged oocytes and relevant mechanisms are still underexplored. Here, we find that supplementation of CoQ10, a natural antioxidant present in human follicular fluids, is able to restore the postovulatory aging-induced fragmentation of oocytes and decline of fertilization. Importantly, we show that CoQ1...
Source: Free Radical Biology and Medicine - August 6, 2019 Category: Biology Authors: Zhang M, ShiYang X, Zhang Y, Miao Y, Chen Y, Cui Z, Xiong B Tags: Free Radic Biol Med Source Type: research

Antibacterial activity of new structural class of semisynthetic molecule, triphenyl-phosphonium conjugated diarylheptanoid.
Abstract Antibiotic resistance in bacteria is a serious threat to public health due to limited therapeutic options. Bactericidal agents with polypharmacological profiles or targeting bacterial membrane have lower propensity to develop resistance. Mitocurcumin (MitoC) is a novel compound synthesized by triphenyl-phosphonium conjugation with curcumin. Here, we demonstrate the antibacterial properties of MitoC that structurally differs markedly from the known antibacterial compounds. MitoC shows efficient bactericidal activity against Gram-positive and Gram-negative bacteria, including Mycobacteria, with MIC values i...
Source: Free Radical Biology and Medicine - August 6, 2019 Category: Biology Authors: Kumari S, Jayakumar S, Gupta GD, Bihani SC, Sharma D, Kutala VK, Sandur SK, Kumar V Tags: Free Radic Biol Med Source Type: research

Glutathione depletion, lipid peroxidation, and the antecedents of ferroptosis: What about cellular calcium ?
PMID: 31398500 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - August 6, 2019 Category: Biology Authors: Pompella A, Maellaro E, Benedetti A, Benedetti A, Casini AF Tags: Free Radic Biol Med Source Type: research

15N-labelled nitrite/nitrate tracer analysis by LC-MS/MS: Urinary and fecal excretion of nitrite/nitrate following oral administration to mice.
Abstract Determination of the modulation of nitrite and nitrate levels in biological samples usually poses a major challenge, owing to their high background concentrations. To effectively investigate the variation of nitrite/nitrate in vivo, in this study, we developed a15N-labelled nitrite/nitrate tracer analysis using LC-MS/MS following the derivatization with 2,3-diaminonaphthalene. This method allows for the determination of 15N-labelled nitrite/nitrate as 15N-2,3-naphthotriazole (15N-NAT) that can efficiently differentiate newly introduced nitrite/nitrate from the background nitrite/nitrate in biological matr...
Source: Free Radical Biology and Medicine - August 6, 2019 Category: Biology Authors: Hu CW, Chang YJ, Yen CC, Chen JL, Muthukumaran RB, Chao MR Tags: Free Radic Biol Med Source Type: research

Redox properties of individual quercetin moieties.
en V, Kuzma M, Trouillas P, Vacek J Abstract Quercetin is one of the most prominent and widely studied flavonoids. Its oxidation has been previously investigated only indirectly by comparative analyses of structurally analogous compounds, e.g. dihydroquercetin (taxifolin). To provide direct evidence about the mechanism of quercetin oxidation, we employed selective alkylation procedures for the step-by-step blocking of individual redox active sites, i.e. the catechol, resorcinol and enol C-3 hydroxyls, as represented by newly prepared quercetin derivatives 1-3. Based on the structure-activity relationship (SAR), el...
Source: Free Radical Biology and Medicine - August 2, 2019 Category: Biology Authors: Heřmánková E, Zatloukalová M, Biler M, Sokolová R, Bancířová M, Tzakos AG, Křen V, Kuzma M, Trouillas P, Vacek J Tags: Free Radic Biol Med Source Type: research

Cholestatic liver disease results increased production of reactive aldehydes and an atypical periportal hepatic antioxidant response.
The objective of this study was to elucidate the impact of cholestatic injury on oxidative stress-related factors. Using hepatic tissue and whole cell liver extracts (LE) isolated from 11-week old C57BL/6J (WT) and Mdr2KO mice, inflammation and oxidative stress was assessed. Concurrently, specific targets of carbonylation were assessed in LE prepared from murine groups as well as from normal and human patients with end-stage PSC. Identified carbonylated proteins were further evaluated using bioinformatics analyses. Picrosirius red staining revealed extensive fibrosis in Mdr2KO liver, and fibrosis colocalized with increased...
Source: Free Radical Biology and Medicine - August 1, 2019 Category: Biology Authors: Shearn CT, Fennimore B, Orlicky DJ, Gao YR, Saba LM, Battista KD, Aivazidis S, Assiri M, Harris PS, Michel C, Merrill GF, Schmidt EE, Colgan SP, Petersen DR Tags: Free Radic Biol Med Source Type: research

Nitration of Drp1 provokes mitophagy activation mediating neuronal injury in experimental autoimmune encephalomyelitis.
Abstract Active autophagy/mitophagy could mediate neurodegeneration and motor disabilities in multiple sclerosis (MS). Mitochondrial recruitment of dynamin-related protein 1 (Drp1) is a crucial step to initiate mitophagy. Peroxynitrite (ONOO-) could be a player in MS pathology but the mechanisms remain unknown. We used animal model of experimental autoimmune encephalomyelitis (EAE) and tested whether ONOO- mediates Drp1 assembly in mitochondria for mitophagy and aggravates MS pathology. We found that autophagy/mitophagy activation was coincidently increased with axonal damage, apoptosis and disease progression in ...
Source: Free Radical Biology and Medicine - August 1, 2019 Category: Biology Authors: Li W, Feng J, Gao C, Wu M, Du Q, Tsoi B, Wang Q, Yang D, Shen J Tags: Free Radic Biol Med Source Type: research

Determination of the effects of torularhodin against alcoholic liver diseases by transcriptome analysis.
Abstract Alcoholic liver disease (ALD) is a major cause of liver injury worldwide. Oxidative damage is one of the main injuries caused by ALD. The aim of this study was to elucidate the preventive effects of torularhodin, extracted from Sporidiobolus pararoseus, on alcoholic liver injury in mice. The mechanisms involved were investigated using transcriptome analysis. Torularhodin supplementation decreased ethanol-induced aspartate transaminase (ALT), aspartate transaminase (AST) and low density lipoprotein (LDL) levels, and increased high density lipoprotein (HDL) levels in the serum of mice. In liver tissue, trea...
Source: Free Radical Biology and Medicine - July 30, 2019 Category: Biology Authors: Li J, Liu C, Guo Y, Pi F, Yao W, Xie Y, Cheng Y, Qian H Tags: Free Radic Biol Med Source Type: research

Associations between socioeconomic status, psychosocial stress, and urinary levels of 8-iso-prostaglandin-F2 α during pregnancy in Puerto Rico.
CONCLUSIONS: Psychosocial stress during pregnancy, as indicated by self-reported questionnaire measures, was not associated with biomarkers of oxidative stress in the PROTECT study. However, results suggest that these biomarkers are elevated among women of lower SES, which is typically associated with stress. Notably, compared to other populations, self-reported psychosocial stress measures were lower in PROTECT compared to other populations. PMID: 31369838 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Eick SM, Meeker JD, Brown P, Swartzendruber A, Rios-McConnell R, Shen Y, Milne GL, Velez-Vega C, Rosario Z, Alshawabkeh A, Cordero JF, Ferguson KK Tags: Free Radic Biol Med Source Type: research

Redox lipidomics and adductomics - advanced analytical strategies to study oxidized lipids and lipid-protein adducts.
PMID: 31369839 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Cruciani G, Domingues P, Fedorova M, Galli F, Spickett CM Tags: Free Radic Biol Med Source Type: research

Plasma cysteine/cystine and glutathione/glutathione disulfide redox potentials in HIV and COPD patients.
Abstract Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined ...
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Watson WH, Ritzenthaler JD, Peyrani P, Wiemken TL, Furmanek S, Reyes Vega AM, Burke TJ, Zheng Y, Ramirez JA, Roman J Tags: Free Radic Biol Med Source Type: research

Post-exercise hypotension and skeletal muscle oxygenation is regulated by nitrate-reducing activity of oral bacteria.
This study investigated whether the nitrate-reducing activity of oral bacteria is a key mechanism to trigger PEH. Following a randomized, double blind and crossover design, twenty-three healthy individuals (15 males/8 females) completed two treadmill trials at moderate intensity. After exercise, participants rinsed their mouth with antibacterial mouthwash to inhibit the activity of oral bacteria or a placebo mouthwash. Blood pressure was measured before, 1 and 2 h after exercise. The microvascular response to a reactive hyperaemia test, as well as, blood and salivary samples were taken before and 2 h after exercise to ...
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Cutler C, Kiernan M, Willis JR, Gallardo-Alfaro L, Casas-Agustench P, White D, Hickson M, Gabaldon T, Bescos R Tags: Free Radic Biol Med Source Type: research

Inhibition of neointima hyperplasia by the combined therapy of linagliptin and metformin via AMPK/Nox4 signaling in diabetic rats.
CONCLUSIONS: We demonstrated that the potential protection of the combined use of linagliptin and metformin on VSMC remodeling through AMPK/Nox4 signal pathway, resulting in the improvement of neointima hyperplasia in diabetic rats. This study provided new therapeutic strategies for vascular stenosis associated with diabetes. PMID: 31369842 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Zhang WX, Tai GJ, Li XX, Xu M Tags: Free Radic Biol Med Source Type: research

Autophagy protects peripheral blood mononuclear cells against inflammation, oxidative and nitrosative stress in diabetic dyslipidemia.
CONCLUSION: Induction of autophagy emerged to be a protective mechanism for the diabetic cells coupled with dyslipidemia. Not only Reactive oxygen species, but also reactive nitrogen species was involved in autophagy induction process. Moreover inhibition study documented, autophagy to have a protective role in pro-inflammatory responses. Thus, enhancing autophagic activity may be an efficient mechanism leading to new therapeutic strategy to restore the glycemic regulation. PMID: 31369843 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 29, 2019 Category: Biology Authors: Chatterjee T, Pattanayak R, Ukil A, Chowdhury S, Bhattacharyya M Tags: Free Radic Biol Med Source Type: research

Alcohol promotes waste clearance in the CNS via brain vascular reactivity.
Abstract The efficient clearance of the interstitial waste metabolites is essential for the normal maintenance of brain homeostasis. The brain lacks the lymphatic clearance system. Thus, the drainage of waste metabolites in the brain is dependent on a slow flow of cerebrospinal fluid (CSF) system. Glymphatic system claims the direct bulk flow transport of small size water-soluble waste metabolites into to the perivenous space by aquaporin-4 water channels of the astrocyte end-feet, but it did not address the diffusive clearance of large size waste metabolites. Here, we addressed the clearance mechanisms of large s...
Source: Free Radical Biology and Medicine - July 27, 2019 Category: Biology Authors: Cheng Y, Liu X, Ma X, Garcia R, Belfield K, Haorah J Tags: Free Radic Biol Med Source Type: research

Mitochondrial oxidative stress-induced transcript variants of ATF3 mediate lipotoxic brain microvascular injury.
Conclusions: TL potentiate ROS by mitochondria which activate mitochondrial oxidative stress, decrease ATP production, increase mitochondrial proton leak and glycolysis rate, and mitochondria DNA damage. Additionally, CPT1A1 siRNA knockdown suppresses oxidative stress and prevents mitochondrial dysfunction and vascular inflammation in TL treated HBMECs. TL activates ATF3-MAPKinase, TNF, and NRF2 signaling pathways. Furthermore, the NRF2 signaling pathway which is upstream of the ATF3-MAPKinase signaling pathway, is also regulated by the mitochondrial oxidative stress. We are the first to report differential inflammatory ch...
Source: Free Radical Biology and Medicine - July 26, 2019 Category: Biology Authors: Nyunt T, Britton M, Wanichthanarak K, Budamagunta M, Voss JC, Wilson DW, Rutledge JC, Aung HH Tags: Free Radic Biol Med Source Type: research

"Oxidative stress in the Perinatal Period".
"Oxidative stress in the Perinatal Period". Free Radic Biol Med. 2019 Jul 25;: Authors: Vento M PMID: 31351951 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 25, 2019 Category: Biology Authors: Vento M Tags: Free Radic Biol Med Source Type: research

Mitohormesis and metabolic health: The interplay between ROS, cAMP and sirtuins.
Abstract The key role of mitochondria in oxidative metabolism and redox homeostasis explains the link between mitochondrial dysfunction and the development of metabolic disorders. Mitochondria's highly dynamic nature, based on alterations in biogenesis, mitophagy, fusion and fission, allows adjusting sequential redox reactions of the electron transport chain (ETC) and dissipation of the membrane potential by ATP synthase, to different environmental cues. With reactive oxygen species being an inevitable by-product of oxidative phosphorylation (OXPHOS), alterations on mitochondrial oxidative rate with a consequent e...
Source: Free Radical Biology and Medicine - July 24, 2019 Category: Biology Authors: Palmeira CM, Teodoro JS, Amorim JA, Steegborn C, Sinclair DA, Rolo AP Tags: Free Radic Biol Med Source Type: research

Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects.
Abstract Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutic...
Source: Free Radical Biology and Medicine - July 24, 2019 Category: Biology Authors: Xia C, Zeng Z, Fang B, Tao M, Gu C, Zheng L, Wang Y, Shi Y, Fang C, Mei S, Chen Q, Zhao J, Lin X, Fan S, Jin Y, Chen P Tags: Free Radic Biol Med Source Type: research

Measuring redox effects on the activities of intracellular proteases such as the 20S Proteasome and the Immuno-Proteasome with fluorogenic peptides.
In this study we analyze different parameters, such as sample concentration, AMC conjugated substrate concentration, duration of assay, and frequency of measurements, and examine how they impact the determination of Proteasome and Immuno-Proteasome activities using fluorogenic peptide substrates. PMID: 31351175 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 24, 2019 Category: Biology Authors: Bonet-Costa V, Sun PY, Davies KJA Tags: Free Radic Biol Med Source Type: research

Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis.
In this study, to gain insights into the molecular mechanisms underpinning the protective effects of loss of GCLM, global profiling of hepatic polar metabolites combined with liver microarray analysis was carried out. These inter-omics analyses revealed both low GSH- and alcohol-driven changes in multiple cellular pathways involving the metabolism of amino acids, fatty acid, glucose and nucleic acids. Notably, several metabolic changes were uniquely present in alcohol-treated Gclm-knockout mouse livers, including acetyl-CoA enrichment and diversion of acetyl-CoA flux from lipogenesis to alterative metabolic pathways, eleva...
Source: Free Radical Biology and Medicine - July 24, 2019 Category: Biology Authors: Chen Y, Manna SK, Golla S, Krausz KW, Cai Y, Garcia-Milian R, Chakraborty T, Chakraborty J, Chatterjee R, Thompson DC, Gonzalez FJ, Vasillou V Tags: Free Radic Biol Med Source Type: research

Serum electrolytes can promote hydroxyl radical-initiated biomolecular damage from inflammation.
Abstract Chronic inflammatory disorders are associated with biomolecular damage attributed partly to reactions with Reactive Oxygen Species (ROS), particularly hydroxyl radicals (•OH). However, the impacts of serum electrolytes on ROS-associated damage has received little attention. We demonstrate that the conversion of •OH to carbonate and halogen radicals via reactions with serum-relevant carbonate and halide concentrations fundamentally alters the targeting of amino acids and loss of enzymatic activity in catalase, albumin and carbonic anhydrase, three important blood proteins. Chemical kinetic modeli...
Source: Free Radical Biology and Medicine - July 23, 2019 Category: Biology Authors: Komaki Y, Simpson AM, Choe JK, Pinney MM, Herschlag D, Chuang YH, Mitch WA Tags: Free Radic Biol Med Source Type: research

S-1-propenylmercaptocysteine protects murine hepatocytes against oxidative stress via persulfidation of Keap1 and activation of Nrf2.
This study provides insights on the potential of CySSPe as an onion-derived dietary agent that modulates redox homeostasis and combats oxidative stress. PMID: 31349040 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 23, 2019 Category: Biology Authors: Tocmo R, Parkin K Tags: Free Radic Biol Med Source Type: research

How did life come to tolerate and thrive in an oxygenated world?
Abstract Looking across our planet's four-and-a-half billion-year history, the rise of dioxygen- an interval sometimes called the Great Oxygenation Event (GOE)-is arguably the most important environmental change. This revolution occurred approximately 2.3 billion years ago, roughly at the mid-way point in Earth history, and it was ultimately driven by a biological innovation: the evolution of oxygenic photosynthesis. The evolution of oxygenic photosynthesis conferred the ability to use water as a photosynthetic substrate (earlier photosynthesis was anoxygenic and required reduced iron, sulfur, carbon, or hydrogen)...
Source: Free Radical Biology and Medicine - July 22, 2019 Category: Biology Authors: Fischer WW, Valentine JS Tags: Free Radic Biol Med Source Type: research

Control and oxidized (DeMP) mitochondrial RNA are proinflammatory regulators in human.
Abstract Inflammation is implicated in a wide range of disorders, and thought to be involved in most leading causes of death today in the United States with high associated costs. New insights into better understanding its etiology, detection and prevention are thus of major importance in health care. One emerging field providing such insights has been the identification of DAMPs, or damage-associated molecular patterns. We have studied DAMPs within the context of degraded and oxidized mitochondrial DNA and RNA ("DeMP"), most recently demonstrating potent mitochondrial RNA (mtRNA) immunogenic response in...
Source: Free Radical Biology and Medicine - July 19, 2019 Category: Biology Authors: Ilic Z, Saxena AR, Periasamy S, Crawford DR Tags: Free Radic Biol Med Source Type: research

l-Serine protects mouse hippocampal neuronal HT22  cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death.
l-Serine protects mouse hippocampal neuronal HT22 cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death. Free Radic Biol Med. 2019 Jul 18;: Authors: Kim KY, Hwang SK, Park SY, Kim MJ, Jun DY, Kim YH Abstract The cytoprotective mechanism of l-serine against oxidative stress-mediated neuronal apoptosis was investigated in mouse hippocampal neuronal HT22 cells. Treatment with the reactive oxygen species (ROS) inducer 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) increased cytosolic and mitochondrial ROS and apoptosis, without necrosis, in HT22 cells. ROS-mediated apoptosis...
Source: Free Radical Biology and Medicine - July 18, 2019 Category: Biology Authors: Kim KY, Hwang SK, Park SY, Kim MJ, Jun DY, Kim YH Tags: Free Radic Biol Med Source Type: research

Modification of endothelial nitric oxide synthase by 4-oxo-2(E)-nonenal(ONE) in preeclamptic placentas.
In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies. PMID: 31323312 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 16, 2019 Category: Biology Authors: Guerby P, Swiader A, Tasta O, Pont F, Rodriguez F, Parant O, Vayssière C, Shibata T, Uchida K, Salvayre R, Negre-Salvayre A Tags: Free Radic Biol Med Source Type: research

Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193.
Abstract Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M-1s-1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP...
Source: Free Radical Biology and Medicine - July 16, 2019 Category: Biology Authors: Randall LM, Rizza JD, Parsonage D, Santos J, Mehl RA, Lowther WT, Poole LB, Denicola A Tags: Free Radic Biol Med Source Type: research

How did the evolution of oxygenic photosynthesis influence the temporal and spatial development of the microbial iron cycle on ancient earth?
yce C Abstract Iron is the most abundant redox active metal on Earth and thus provides one of the most important records of the redox state of Earth's ancient atmosphere, oceans and landmasses over geological time. The most dramatic shifts in the Earth's iron cycle occurred during the oxidation of Earth's atmosphere. However, tracking the spatial and temporal development of the iron cycle is complicated by uncertainties about both the timing and location of the evolution of oxygenic photosynthesis, and by the myriad of microbial processes that act to cycle iron between redox states. In this review, we piece togeth...
Source: Free Radical Biology and Medicine - July 16, 2019 Category: Biology Authors: Schad M, Konhauser KO, Sánchez-Baracaldo P, Kappler A, Bryce C Tags: Free Radic Biol Med Source Type: research

Xenobiotic mediated diabetogenesis: Developmental exposure to dichlorvos or atrazine leads to type 1 or type 2 diabetes in drosophila.
Abstract The increased incidence of Diabetes to the magnitude of a global epidemic is attributed to non-traditional risk factors, including exposure to environmental chemicals. However, the contribution of xenobiotic exposure during the development of an organism to the etiology of diabetes is not fully addressed. Developing stages are more susceptible to chemical insult, but knowledge on the consequence of the same to the onset of diabetes is residual. In this context, by using Drosophila melanogaster having conserved Insulin/Insulin growth factor-like signaling (IIS) as well as glucose homeostasis as a model, we...
Source: Free Radical Biology and Medicine - July 15, 2019 Category: Biology Authors: Gupta HP, Jha RR, Ahmad H, Patel DK, Ram KR Tags: Free Radic Biol Med Source Type: research

Molecular mechanism for the activation of the anti-tuberculosis drug isoniazid by Mn(III): First detection and unequivocal identification of the critical N-centered isoniazidyl radical and its exact location.
This study represents the first detection and unequivocal identification of the initial N-centered isoniazidyl radical and its exact location. These findings should provide a new perspective on the molecular mechanism of INH activation, which may have broad biomedical and toxicological significance for future research for more efficient hydrazide anti-tuberculosis drugs. PMID: 31319159 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 15, 2019 Category: Biology Authors: Qin L, Huang CH, Xu D, Xie LN, Shao J, Mao L, Kalyanaraman B, Zhu BZ Tags: Free Radic Biol Med Source Type: research

Age-dependent dysregulation of redox genes may contribute to fibrotic pulmonary disease susceptibility.
Abstract Aging is associated with enhanced oxidative stress and increased susceptibility to numerous diseases. This relationship is particularly striking with respect to the incidence of fibrotic lung disease. To identify potential mechanisms underlying the association between aging and susceptibility to fibrotic lung disease we analyzed transcriptome data from 342 disease-free human lung samples as a function of donor age. Our analysis reveals that aging in lung is accompanied by modest yet progressive changes in genes modulating redox homeostasis, the TGF-beta 1 signaling axis, and the extracellular matrix (ECM)...
Source: Free Radical Biology and Medicine - July 14, 2019 Category: Biology Authors: Elko E, Mahoney JM, Vacek P, van der Vilet A, Anathy V, van der Velden JLJL, Janssen-Heininger YMW, Seward DJ Tags: Free Radic Biol Med Source Type: research

miR-15b induces premature ovarian failure in mice via inhibition of α-Klotho expression in ovarian granulosa cells.
miR-15b induces premature ovarian failure in mice via inhibition of α-Klotho expression in ovarian granulosa cells. Free Radic Biol Med. 2019 Jul 13;: Authors: Liu T, Liu Y, Huang Y, Chen J, Yu Z, Chen C, Lai L Abstract A thorough understanding of epigenetics regulatory mechanisms of premature ovarian failure (POF) is still lacking. Here, we found that cyclophosphamide induced significantly decrease in α-Klotho (Kl) expression in mouse ovarian granulosa cells (mOGCs), suggesting that cyclophosphamide inhibited Kl expression. Cyclophosphamide also significantly accelerated ageing and led to...
Source: Free Radical Biology and Medicine - July 13, 2019 Category: Biology Authors: Liu T, Liu Y, Huang Y, Chen J, Yu Z, Chen C, Lai L Tags: Free Radic Biol Med Source Type: research

Redox states of hemoglobin determine left ventricle pressure recovery and activity of mitochondrial complex IV in hypoxic rat hearts.
Abstract Cardiovascular effects were reported to occur in humans and in animal models during transfusion with hemoglobin (Hb)-based oxygen therapeutics. The effects of Hb's iron redox states on cardiac parameters during hypoxia/reoxygenation are however poorly defined. We hypothesize that acute exposures to ferric Hb during hypoxia leads to cardiomyocyte injury and an impaired left ventricular response accompanied by cardiac mitochondrial bioenergetic dysfunction. Recovery of left ventricular functions in an isolated rat heart Langendorff perfusion system was observed following perfusion with ferrous but not with ...
Source: Free Radical Biology and Medicine - July 11, 2019 Category: Biology Authors: Edmondson M, Jana S, Meng F, Strader MB, Baek JH, Gao Y, Buehler PW, Alayash AI Tags: Free Radic Biol Med Source Type: research

An unexpected new pathway for nitroxide radical production via more reactve nitrogen-centered amidyl radical intermediate during detoxification of the carcinogenic halogenated quinones by N-alkyl hydroxamic acids.
This study represents the first report of an unexpected new pathway for nitroxide radical production via hydrogen abstration reaction of a more reactive amidyl radical intermediate during the detoxification of the carcinogenic polyhalogenated quinones by N-alkyl hydroxamic acids, which provides more direct experimental evidence to better explain not only our previous finding that excess DFO can provide effective but only partial protection against TCHQ (or TCBQ)-induced biological damage, and also the potential side-toxic effects induced by DFO and other N-alkyl hydroxamic acid drugs. PMID: 31302229 [PubMed - as suppl...
Source: Free Radical Biology and Medicine - July 11, 2019 Category: Biology Authors: Xu D, Huang CH, Qin L, Xie LN, Mao L, Shao J, Kalyanaraman B, Zhu BZ Tags: Free Radic Biol Med Source Type: research

S-Glutathionylation of mouse selenoprotein W prevents oxidative stress-induced cell death by blocking the formation of an intramolecular disulfide bond.
In this study, using purified recombinant SELENOW in which Sec13 was changed to Cys, we found that SELENOW was glutathionylated at Cys33 and that this S-glutathionylation was enhanced by oxidative stress. We also found that the S-glutathionylation of SELENOW at Cys33 in HEK293 cells was due to glutathione S-transferase Pi (GSTpi) and that this modification was reversed by glutaredoxin1 (Grx1). In addition to the disulfide bond between the Cys10 and Cys13 of SELENOW, a second disulfide bond was formed between Cys33 and Cys87 under oxidative stress conditions. The second disulfide bond was reduced by Trx1, but the disulfid...
Source: Free Radical Biology and Medicine - July 9, 2019 Category: Biology Authors: Ko KY, Lee JH, Jang JK, Jin Y, Kang H, Kim IY Tags: Free Radic Biol Med Source Type: research

Plin5 deficiency exacerbates pressure overload-induced cardiac hypertrophy and heart failure by enhancing myocardial fatty acid oxidation and oxidative stress.
In conclusion, Plin5 deficiency increases myocardial lipolysis, elevates FAO and oxidative burden, and thereby exacerbates cardiac hypertrophy and heart failure in TAC-treated mice. PMID: 31291602 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 7, 2019 Category: Biology Authors: Wang C, Yuan Y, Wu J, Zhao Y, Gao X, Chen Y, Sun C, Xiao L, Zheng P, Hu P, Li Z, Wang Z, Ye J, Zhang L Tags: Free Radic Biol Med Source Type: research

Hydroxytyrosol prevents PM2.5-induced adiposity and insulin resistance by restraining oxidative stress related NF- κB pathway and modulation of gut microbiota in a murine model.
Hydroxytyrosol prevents PM2.5-induced adiposity and insulin resistance by restraining oxidative stress related NF-κB pathway and modulation of gut microbiota in a murine model. Free Radic Biol Med. 2019 Jul 04;: Authors: Wang N, Ma Y, Liu Z, Liu L, Yang K, Wei Y, Liu Y, Chen X, Sun X, Wen D Abstract Exposure to fine particular matter (≤2.5 μM, PM2.5) contributes to increased risk of obesity and type 2 diabetes. Hydroxytyrosol (HT), a simple polyphenol found in virgin olive oil, is considered to be beneficial for cardiovascular and metabolic disorders. The current study determined whether...
Source: Free Radical Biology and Medicine - July 4, 2019 Category: Biology Authors: Wang N, Ma Y, Liu Z, Liu L, Yang K, Wei Y, Liu Y, Chen X, Sun X, Wen D Tags: Free Radic Biol Med Source Type: research

Dimethyl fumarate alters intracellular Ca2+ handling in immune cells by redox-mediated pleiotropic effects.
r A Abstract Dimethyl fumarate (DMF) is widely used to treat the human autoimmune diseases multiple sclerosis (MS) and psoriasis. DMF causes short-term oxidative stress and activates the antioxidant response via the transcription factor Nrf2 but its immunosuppressive effect is not well understood. Immune cell activation depends on calcium signaling which itself is influenced by the cellular redox state. We therefore measured calcium, reactive oxygen species levels and glutathione content in lymphocytes from immunized mice before onset of experimental autoimmune encephalomyelitis, in peripheral blood mononuclear ce...
Source: Free Radical Biology and Medicine - July 4, 2019 Category: Biology Authors: Herrmann AK, Wüllner V, Moos S, Graf J, Chen J, Kieseier B, Kurschus FC, Albrecht P, Vangheluwe P, Methner A Tags: Free Radic Biol Med Source Type: research

The myeloperoxidase product, hypochlorous acid, reduces thrombus formation under flow and attenuates clot retraction and fibrinolysis in human blood.
PMID: 31279970 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 4, 2019 Category: Biology Authors: Misztal T, Golaszewska A, Tomasiak-Lozowska MM, Iwanicka M, Marcinczyk N, Leszczynska A, Chabielska E, Rusak T Tags: Free Radic Biol Med Source Type: research

Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1 α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE.
In conclusion, our data demonstrated that ghrelin reduced oxidative stress injury and neuronal apoptosis which was in part via the GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 signalling pathway after HI. Ghrelin may be a novel therapeutic target for treatment after neonatasl HI injury. PMID: 31279091 [PubMed - as supplied by publisher] (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - July 3, 2019 Category: Biology Authors: Huang J, Liu W, Doycheva DM, Gamdzyk M, Lu W, Tang J, Zhang JH Tags: Free Radic Biol Med Source Type: research