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Free Radical Biology & Medicine

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https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#1
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28807817/assessment-of-glutathione-glutathione-disulphide-ratio-and-s-glutathionylated-proteins-in-human-blood-solid-tissues-and-cultured-cells
#2
REVIEW
Daniela Giustarini, Graziano Colombo, Maria Lisa Garavaglia, Emanuela Astori, Nicola Marcello Portinaro, Francesco Reggiani, Salvatore Badalamenti, Anna Maria Aloisi, Annalisa Santucci, Ranieri Rossi, Aldo Milzani, Isabella Dalle-Donne
Glutathione (GSH) is the major non-protein thiol in humans and other mammals, which is present in millimolar concentrations within cells, but at much lower concentrations in the blood plasma. GSH and GSH-related enzymes act both to prevent oxidative damage and to detoxify electrophiles. Under oxidative stress, two GSH molecules become linked by a disulphide bridge to form glutathione disulphide (GSSG). Therefore, assessment of the GSH/GSSG ratio may provide an estimation of cellular redox metabolism. Current evidence resulting from studies in human blood, solid tissues, and cultured cells suggests that GSH also plays a prominent role in protein redox regulation via S-glutathionylation, i...
August 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28807816/mtor-in-down-syndrome-role-in-a%C3%A3-and-tau-neuropathology-and-transition-to-alzheimer-disease-like-dementia
#3
REVIEW
Fabio Di Domenico, Antonella Tramutola, Cesira Foppoli, Elisabeth Head, Marzia Perluigi, D Allan Butterfield
The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS)...
August 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28807815/bcl-xl-knockout-attenuates-mitochondrial-respiration-and-causes-oxidative-stress-that-is-compensated-by-pentose-phosphate-pathway-activity
#4
Annika Pfeiffer, Julia Schneider, Diones Bueno, Amalia Dolga, Timo-Daniel Voss, Jan Lewerenz, Verena Wüllner, Axel Methner
Bcl-xL is an anti-apoptotic protein that localizes to the outer mitochondrial membrane and influences mitochondrial bioenergetics by controlling Ca(2+) influx into mitochondria. Here, we analyzed the effect of mitochondrial Bcl-xL on mitochondrial shape and function in knockout (KO), wildtype and rescued mouse embryonic fibroblast cell lines. Mitochondria of KO cells were more fragmented, exhibited a reduced ATP concentration, and reduced oxidative phosphorylation (OXPHOS) suggesting an increased importance of ATP generation by other means...
August 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28801243/peroxiredoxin-2-plays-a-pivotal-role-as-multimodal-cytoprotector-in-the-early-phase-of-pulmonary-hypertension
#5
Enrica Federti, Alessandro Matte', Alessandra Ghigo, Immacolata Andolfo, Cimino James, Angela Siciliano, Christophe Leboeuf, Anne Janin, Francesco Manna, Soo Young Choi, Achille Iolascon, Elisabetta Beneduce, Davide Melisi, Dae Won Kim, Sonia Levi, Lucia De Franceschi
Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homestasis is yet to be fully defined. Here, we showed that Prx2(-/-) mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH...
August 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28801242/oxidant-species-are-involved-in-t-b-mediated-erk1-2-phosphorylation-that-activates-p53-p21-axis-to-promote-kshv-lytic-cycle-in-pel-cells
#6
Roberta Gonnella, Shivangi Yadav, Maria Saveria Gilardini Montani, Marisa Granato, Roberta Santarelli, Alessia Garufi, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
KSHV is a gammaherpesvirus strongly associated to human cancers such as Primary Effusion Lymphoma (PEL) and Kaposi's Sarcoma. The naturally virus-infected tumor cells usually display latent infection since a minority of cells undergoes spontaneous viral replication. The lytic cycle can be induced in vitro upon appropriate stimuli such as TPA (T), alone or in combination with butyrate (B), (T/B). In previous studies, Protein Kinase C (PKC) δ, Extracellular Signal-regulated Kinase1/2 (ERK1/2) and p53-p21 axis have been separately reported to play a role in KSHV reactivation from latency...
August 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28790013/chronic-vitamin-e-deficiency-impairs-cognitive-function-in-adult-zebrafish-via-dysregulation-of-brain-lipids-and-energy-metabolism
#7
Melissa McDougall, Jaewoo Choi, Kathy Magnusson, Lisa Truong, Robert Tanguay, Maret G Traber
Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E-) or VitE-sufficient (E+)...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28790012/mdivi-1-ameliorates-early-brain-injury-after-subarachnoid-hemorrhage-via-the-suppression-of-inflammation-related-blood-brain-barrier-disruption-and-endoplasmic-reticulum-stress-based-apoptosis
#8
Lin-Feng Fan, Ping-You He, Yu-Cong Peng, Qing-Hua Du, Yi-Jun Ma, Jian-Xiang Jin, Hang-Zhe Xu, Jian-Ru Li, Zhi-Jiang Wang, Sheng-Long Cao, Tao Li, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28782644/dmapt-inhibits-nf-%C3%AE%C2%BAb-activity-and-increases-sensitivity-of-prostate-cancer-cells-to-x-rays-in-vitro-and-in-tumor-xenografts-in-vivo
#9
Marc S Mendonca, William T Turchan, Melanie E Alpuche, Christopher N Watson, Neil C Estabrook, Helen Chin-Sinex, Jeremy B Shapiro, Imade E Imasuen-Williams, Gabriel Rangel, David P Gilley, Nazmul Huda, Peter A Crooks, Ronald H Shapiro
Constitutive activation of the pro-survival transcription factor NF-κB has been associated with resistance to both chemotherapy and radiation therapy in many human cancers, including prostate cancer. Our lab and others have demonstrated that the natural product parthenolide can inhibit NF-κB activity and sensitize PC-3 prostate cancers cells to X-rays in vitro; however, parthenolide has poor bioavailability in vivo and therefore has little clinical utility in this regard. We show here that treatment of PC-3 and DU145 human prostate cancer cells with dimethylaminoparthenolide (DMAPT), a parthenolide derivative with increased bioavailability, inhibits constitutive and radiation-induced NF-κB binding activity and slows prostate cancer cell growth...
August 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28778483/intermittent-hypoxia-induced-cardiomyopathy-and-its-prevention-by-nrf2-and-metallothionein
#10
Shanshan Zhou, Xia Yin, Jingpeng Jin, Yi Tan, Daniel J Conklin, Ying Xin, Zhiguo Zhang, Weixia Sun, Taixing Cui, Jun Cai, Yang Zheng, Lu Cai
The mechanism for intermittent hypoxia (IH)-induced cardiomyopathy remains obscure. We reported the prevention of acute and chronic IH-induced cardiac damage by selective cardiac overexpression of metallothionein (MT). Herein we defined that MT-mediated protection from IH-cardiomyopathy is via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a critical redox-balance controller in the body. For this, mice were exposed to IH for 3 days (acute) or 4 or 8 weeks (chronic). Cardiac Nrf2 and MT expression in response to IH were significantly increased acutely yet decreased chronically...
August 2, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28778482/importance-of-nadph-oxidase-mediated-redox-signaling-in-the-detrimental-effect-of-crp-on-pancreatic-insulin-secretion
#11
Pei-Chi Chan, Ya-Chin Wang, Yi-Ling Chen, Wan-Ning Hsu, Yu-Feng Tian, Po-Shiuan Hsieh
Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells...
August 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28774816/redox-regulation-of-the-tumor-suppressor-pten-by-the-thioredoxin-system-and-cumene-hydroperoxide
#12
Seong-Jeong Han, Ying Zhang, Inyoung Kim, Kee-Oh Chay, Hyun Joong Yoon, Dong Il Jang, Sung Yeul Yang, Jiyoung Park, Hyun Ae Woo, Iha Park, Seung-Rock Lee
Intracellular redox status influences the oxidation and enzyme activity of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN). Cumene hydroperoxide (CuHP), an organic hydroperoxide, is a known tumor promoter. However, molecular targets and action mechanism of CuHP in tumor promotion have not been well characterized. In this study, we investigated the effect of CuHP on the redox state of PTEN in HeLa cells. In addition, the intracellular reducing system of oxidized PTEN was analyzed using a biochemical approach and the effect of CuHP on this reducing system was also analyzed...
August 1, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28774817/euphorbia-factor-l1-inhibits-osteoclastogenesis-by-regulating-cellular-redox-status-and-induces-fas-mediated-apoptosis-in-osteoclast
#13
Seong-Eun Hong, Jiae Lee, Dong-Hyun Seo, Hye In Lee, Doo Ri Park, Gong-Rak Lee, You-Jin Jo, Narae Kim, Minjung Kwon, Hansem Shon, Eun Kyoung Seo, Han-Sung Kim, Soo Young Lee, Woojin Jeong
Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages...
July 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28774815/antioxidant-defense-in-quiescent-cells-determines-selectivity-of-electron-transport-chain-inhibition-induced-cell-death
#14
Jan Blecha, Silvia Magalhaes Novais, Katerina Rohlenova, Eliska Novotna, Sandra Lettlova, Sabine Schmitt, Hans Zischka, Jiri Neuzil, Jakub Rohlena
Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting...
July 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28757400/epigenetic-regulation-of-ec-sod-expression-in-aging-lung-fibroblasts-role-of-histone-acetylation
#15
Jesse Roman, Jianxin Zhu, Jeffrey D Ritzenthaler, Igor N Zelko
Lung disorders characterized by fibroproliferation and excessive deposition of extracellular matrices occur in late adulthood, and their pathological manifestations become more prominent with aging. The exact mechanisms linking aging and fibroproliferative disorders are unknown, but increased oxidative stress resulting in the accumulation of damaged proteins, DNA, and lipids is considered a major factor. In the lung, and especially in the pulmonary fibroblasts, the extracellular superoxide dismutase (EC-SOD) is a major antioxidant enzyme that has been implicated in pulmonary fibrosing disorders, among others...
July 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28756312/hydrogen-peroxide-nitric-oxide-and-atp-are-molecules-involved-in-cardiac-mitochondrial-biogenesis-in-diabetes
#16
Silvina S Bombicino, Darío E Iglesias, Ivana A Rukavina-Mikusic, Bruno Buchholz, Ricardo J Gelpi, Alberto Boveris, Laura B Valdez
This study, in an experimental model of type I Diabetes Mellitus in rats, deals with the mitochondrial production rates and steady-state concentrations of H2O2 and NO, and ATP levels as part of a network of signaling molecules involved in heart mitochondrial biogenesis. Sustained hyperglycemia leads to a cardiac compromise against a work overload, in the absence of changes in resting cardiac performance and of heart hypertrophy. Diabetes was induced in male Wistar rats by a single dose of Streptozotocin (STZ, 60mg × kg(-1), ip...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28756311/neurogenesis-impairment-an-early-developmental-defect-in-down-syndrome
#17
REVIEW
Fiorenza Stagni, Andrea Giacomini, Marco Emili, Sandra Guidi, Renata Bartesaghi
Down syndrome (DS) is characterized by brain hypotrophy and intellectual disability starting from early life stages. Accumulating evidence shows that the phenotypic features of the DS brain can be traced back to the fetal period since the DS brain exhibits proliferation potency reduction starting from the critical time window of fetal neurogenesis. This defect is worsened by the fact that neural progenitor cells exhibit reduced acquisition of a neuronal phenotype and an increase in the acquisition of an astrocytic phenotype...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28756310/peroxyl-radical-and-photo-oxidation-of-glucose-6-phosphate-dehydrogenase-generates-cross-links-and-functional-changes-via-oxidation-of-tyrosine-and-tryptophan-residues
#18
Fabian Leinisch, Michele Mariotti, Martin Rykaer, Camilo Lopez-Alarcon, Per Hägglund, Michael J Davies
Protein oxidation is a frequent event as a result of the high abundance of proteins in biological samples and the multiple processes that generate oxidants. The reactions that occur are complex and poorly understood, but can generate major structural and functional changes on proteins. Current data indicate that pathophysiological processes and multiple human diseases are associated with the accumulation of damaged proteins. In this study we investigated the mechanisms and consequences of exposure of the key metabolic enzyme glucose-6-phosphate dehydrogenase (G6PDH) to peroxyl radicals (ROO(•)) and singlet oxygen ((1)O2), with particular emphasis on the role of Trp and Tyr residues in protein cross-linking and fragmentation...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28756309/activation-of-brain-glucose-metabolism-ameliorating-cognitive-impairment-in-app-ps1-transgenic-mice-by-electroacupuncture
#19
Weilin Liu, Peiyuan Zhuo, Long Li, Hao Jin, Bingbing Lin, Yingzheng Zhang, Shengxiang Liang, Jie Wu, Jia Huang, Zhifu Wang, Ruhui Lin, Lidian Chen, Jing Tao
An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal (18)F-Fluoro-2-deoxy-D-Glucose ((18)F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28754499/fructose-induced-neurogenic-hypertension-mediated-by-overactivation-of-p38-mapk-to-impair-insulin-signaling-transduction-caused-central-insulin-resistance
#20
Pei-Wen Cheng, Yu-Te Lin, Wen-Yu Ho, Pei-Jung Lu, Hsin-Hung Chen, Chi-Cheng Lai, Gwo-Ching Sun, Tung-Chen Yeh, Michael Hsiao, Ching-Jiunn Tseng, Chun-Peng Liu
Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group...
July 25, 2017: Free Radical Biology & Medicine
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