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Free Radical Biology & Medicine

Omar Emiliano Aparicio-Trejo, Laura María Reyes-Fermín, Alfredo Briones-Herrera, Edilia Tapia, Carlos León-Contreras, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, José Pedraza-Chaverri
Folic acid (FA)-induced acute kidney injury (AKI) is a widely used model for studies of the renal damage and its progression to chronic state. However, the molecular mechanisms by which FA induces AKI remain poorly understood. Since renal function depends on mitochondrial homeostasis, it has been suggested that mitochondrial alterations contribute to AKI development. Additionally, N-acetyl-cysteine (NAC) can be a protective agent to prevent mitochondrial and renal dysfunction in this model, given its ability to increase mitochondrial glutathione (GSH) and to control the S-glutathionylation levels, a reversible post-translational modification that has emerged as a mechanism able to link mitochondrial energy metabolism and redox homeostasis...
November 12, 2018: Free Radical Biology & Medicine
Swati Khole, Smriti Mittal, Nidhi Jagadish, Debjani Ghosh, Vijay Gadgil, Vilas Sinkar, Saroj Ghaskadbi
Andrographis paniculata Nees and its principal compound andrographolide are well known for exerting beneficial effects by modulating signaling pathways in different biological systems. Our earlier studies have demonstrated the ability of andrographolide as well as andrographolide enriched extracts to activate Nrf2/HO-1 pathway through adenosine A2a receptor. Present study investigated ability of andrographolide to regulate Nrf2 induced antioxidant defense systems by miRNAs using HepG2 cells. Andrographolide strongly induced Nrf2 which in turn modulated enzymes of glutathione and thioredoxin antioxidant systems...
November 8, 2018: Free Radical Biology & Medicine
Ji Young Oh, Gee Euhn Choi, Hyun Jik Lee, Young Hyun Jung, Chang Woo Chae, Jun Sung Kim, Chang-Kyu Lee, Ho Jae Han
17β-Estradiol (E2) is an important regulator of energy homeostasis and glucose metabolism, thus making it a potential target for preventing or treating metabolic disorders. However, the exact mechanism by which E2 affects high glucose-induced oxidative stress remains unclear. Therefore, the present study investigated the role of E2 in high glucose-induced mitochondrial reactive oxygen species (mtROS) production through estrogen receptor (ER)-mediated signaling in human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in vitro...
November 6, 2018: Free Radical Biology & Medicine
Elen Rizzi, Jefferson H Amaral, Danielle A Guimarães, Sandra O Conde-Tella, Lucas C Pinheiro, Raquel F Gerlach, Michele M Castro, Jose E Tanus-Santos
Hypertension is associated with cardiovascular remodeling. Given that impaired redox state activates matrix metalloproteinase (MMP)- 2 and promotes vascular remodeling, we hypothesized that nitrite treatment at a non-antihypertensive dose exerts antioxidant effects and attenuates both MMP-2 activation and vascular remodeling of hypertension. We examined the effects of oral sodium nitrite at antihypertensive (15 mg/kg) or non-antihypertensive (1 mg/kg) daily dose in hypertensive rats (two kidney, one clip; 2K1C model)...
November 3, 2018: Free Radical Biology & Medicine
Axelle Hoge, Michèle Guillaume, Adelin Albert, Jessica Tabart, Nadia Dardenne, Anne-Françoise Donneau, Claire Kevers, Jean-Olivier Defraigne, Joël Pincemail
When conducting research on polyphenols and their effects on health, it is of primary importance to use standardised and validated dietary assessment tools. This paper aims at assessing the validity of a food frequency questionnaire (FFQ) for quantifying dietary polyphenol exposure among healthy adults using the method of triads. Fifty-three healthy adults, aged 20-60, were included in the study. Total dietary polyphenol intake (TDP) estimated by the FFQ was compared with TDP measured by a 3-day food record (FR) and with urinary excretion levels of total polyphenols (TUP)...
November 3, 2018: Free Radical Biology & Medicine
Peng-Cheng Fan, Yao Zhang, Yu Wang, Wei Wei, Yan-Xia Zhou, Yi Xie, Xin Wang, Ying-Zi Qi, Lei Chang, Zheng-Ping Jia, Zhe Zhou, Hua Guan, Hong Zhang, Ping Xu, Ping-Kun Zhou
Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with identifier PXD008351...
November 2, 2018: Free Radical Biology & Medicine
Dongwook Yeo, Chounghun Kang, Mari Carmen Gomez-Cabrera, Jose Vina, Li Li Ji
Mitochondrial dysfunction plays an important role in the etiology of age-related muscle atrophy known as sarcopenia. PGC-1α is positioned at the center of crosstalk in regulating mitochondrial quality control, but its role in mitophagy in aged skeletal muscle is currently unclear. The present study investigated the effects of aging and PGC-1α overexpression via in vivo DNA transfection on key mitophagy protein markers, as well as mitochondrial dynamics related proteins, metabolic function and antioxidant capacity in mouse muscle...
November 2, 2018: Free Radical Biology & Medicine
Rina Kato, Masataka Hayashi, Toshihiro Aiuchi, Naoko Sawada, Takashi Obama, Hiroyuki Itabe
The events that trigger early onset of atherosclerotic lesion formation are poorly understood. Initially, microscopic atherosclerotic lesions appear in the aortic root in 10-week-old apoE-knockout mice that are fed normal chow. Using proteome and immunohistochemical analyses, we investigated proteins in aortic media whose expression changes in athero-prone regions at the beginning of lesion formation. Protein profiles of the root/arch and thoracic/abdominal regions of aortas in 10-week-old apoE-knockout mice were analyzed using 2D-gel electrophoresis...
November 2, 2018: Free Radical Biology & Medicine
Manoj Paul, Mahadevappa Hemshekhar, Kempaiah Kemparaju, Kesturu S Girish
Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted...
November 2, 2018: Free Radical Biology & Medicine
María Inés De Armas, Romina Esteves, Nicolás Viera, Aníbal M Reyes, Mauricio Mastrogiovanni, Thiago G P Alegria, Luis E S Netto, Verónica Tórtora, Rafael Radi, Madia Trujillo
Mitochondria are main sites of peroxynitrite formation. While at low concentrations mitochondrial peroxynitrite has been associated with redox signaling actions, increased levels can disrupt mitochondrial homeostasis and lead to pathology. Peroxiredoxin 3 is exclusively located in mitochondria, where it has been previously shown to play a major role in hydrogen peroxide reduction. In turn, reduction of peroxynitrite by peroxiredoxin 3 has been inferred from its protective actions against tyrosine nitration and neurotoxicity in animal models, but was not experimentally addressed so far...
November 1, 2018: Free Radical Biology & Medicine
Ken-Ichiro Matsumoto, James B Mitchell, Murali C Krishna
Nitroxide free radicals can serve as redox-sensitive MRI contrast agents useful to image the redox status of tissue of interest. In this study, the effect of oxygen content in the inspired gas on the kinetics of metabolism of three nitroxides has been evaluated in the muscle and tumor in mice. SCC tumors (approximate size of 1.0cm3 ) on the right hind leg of female C3H/Hen MTV- mice were prepared. Three nitroxides, 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), and 4-hydroxy-tetramethylpiperidine-N-oxyl (TEMPOL), having different lipophilicities were compared using MR redox imaging...
November 1, 2018: Free Radical Biology & Medicine
Zhao Wei, Haiyang Guo, Junchao Qin, Shihua Lu, Qiao Liu, Xiyu Zhang, Yongxin Zou, Yaoqin Gong, Changshun Shao
Cellular senescence, an irreversible proliferative arrest, functions in tissue remodeling during development and is implicated in multiple aging-associated diseases. While senescent cells often manifest an array of senescence-associated phenotypes, such as cell cycle arrest, altered heterochromatin architecture, reprogrammed metabolism and senescence-associated secretory phenotype (SASP), the identification of senescence cells has been hindered by lack of specific and universal biomarkers. To systematically identify universal biomarkers of cellular senescence, we integrated multiple transcriptome data sets of senescent cells obtained through different in vitro manipulation modes as well as age-related gene expression data of human tissues...
November 1, 2018: Free Radical Biology & Medicine
Martin Lee, Christine Wang, Steven W Jin, Mark P Labrecque, Timothy V Beischlag, Mark A Brockman, Jonathan C Choy
The production of nitric oxide (NO) by inducible NO synthase (iNOS) and the regulation of gene expression by hypoxia-inducible factors (HIFs) are important for many aspects of human cell biology. However, little is known about whether iNOS expression is controlled by HIFs in human cells. Stimulation of A549 human lung epithelial cells with cytokines (TNF, IL-1 and IFNγ) increased the nuclear accumulation of HIF-1 in normoxic conditions. Activation of HIF-1 by hypoxia or CoCl2 was not sufficient to induce iNOS expression...
November 1, 2018: Free Radical Biology & Medicine
Issa Olakunle Yusuf, Hsiu-Mei Chen, Pei-Hsun Cheng, Chih-Yi Chang, Shaw-Jenq Tsai, Jih-Ing Chuang, Chia-Ching Wu, Bu-Miin Huang, H Sunny Sun, Shang-Hsun Yang
Huntington's disease (HD) is a heritable neurodegenerative disorder, and has been characterized as an increase of oxidative stress in brain regions. In our previous results, we showed fibroblast growth factor 9 (FGF9) provides neuroprotective functions to suppress cell death in HD striatal cells dominantly through ERK signalling. However, whether the working mechanism of FGF9 is related to anti-oxidative stress in HD is still unknown. In this study, STHdhQ7/Q7 (Q7) and STHdhQ111/Q111 (Q111) striatal knock-in cell lines were used to examine the neuroprotective effects of FGF9 against oxidative stress in HD...
November 1, 2018: Free Radical Biology & Medicine
Alberto Cruz-Bermúdez, Raquel Laza-Briviesca, Ramiro J Vicente-Blanco, Aránzazu García-Grande, Maria José Coronado, Sara Laine-Menéndez, Cristina Alfaro, Juan Cristobal Sanchez, Fernando Franco, Virginia Calvo, Atocha Romero, Paloma Martin-Acosta, Clara Salas, José Miguel Garcia, Mariano Provencio
Lung cancer is a major public health problem due to its high incidence and mortality rate. The altered metabolism in lung cancer is key for the diagnosis and has implications on both, the prognosis and the response to treatments. Although Cancer-associated fibroblasts (CAFs) are one of the major components of the tumor microenvironment, little is known about their role in lung cancer metabolism. We studied tumor biopsies from a cohort of 12 stage IIIA lung adenocarcinoma patients and saw a positive correlation between the grade of fibrosis and the glycolysis phenotype (Low PGC-1α and High GAPDH/MT-CO1 ratio mRNA levels)...
November 1, 2018: Free Radical Biology & Medicine
Hoi-Shan Wong, Bérengère Benoit, Martin D Brand
The relative contributions of different mitochondrial and cytosolic sources of superoxide and hydrogen peroxide in cells are not well established because of a lack of suitable quantitative assays. To address this problem using resting C2C12 myoblasts we measured the effects of specific inhibitors that do not affect other pathways on the rate of appearance of hydrogen peroxide in the extracellular medium. We used inhibitors of NADPH oxidases (NOXs), suppressors of site IQ electron leak (S1QELs) at mitochondrial Complex I, and suppressors of site IIIQo electron leak (S3QELs) at mitochondrial Complex III...
October 31, 2018: Free Radical Biology & Medicine
Daria M Svistunova, Jillian N Simon, Elzbieta Rembeza, Mark Crabtree, Wyatt W Yue, Peter L Oliver, Mattéa J Finelli
Protein aggregation, oxidative and nitrosative stress are etiological factors common to all major neurodegenerative disorders. Therefore, identifying proteins that function at the crossroads of these essential pathways may provide novel targets for therapy. Oxidation resistance 1 (Oxr1) is a protein proven to be neuroprotective against oxidative stress, although the molecular mechanisms involved remain unclear. Here, we demonstrate that Oxr1 interacts with the multifunctional protein, peroxiredoxin 2 (Prdx2), a potent antioxidant enzyme highly expressed in the brain that can also act as a molecular chaperone...
October 31, 2018: Free Radical Biology & Medicine
Wei Feng, Tong Lei, Yue Wang, Run Feng, Juntao Yuan, Xiyue Shen, Yongguang Wu, Junling Gao, Wenjun Ding, Zhongbing Lu
Excessive myocardial lipid accumulation is a major feature of diabetic cardiomyopathy (DCM). Although general control nonderepressible 2 (GCN2) has been identified as a sensor of amino acid availability, it also functions as an important regulator of hepatic lipid metabolism. Our previous studies have reported that GCN2 promotes pressure overload or doxorubicin-induced cardiac dysfunction by increasing cardiomyocyte apoptosis and myocardial oxidative stress. However, the impact of GCN2 on the development of DCM remains unclear...
October 30, 2018: Free Radical Biology & Medicine
Brígida R Pinho, Sara D Reis, Richard C Hartley, Michael P Murphy, Jorge M A Oliveira
Superoxide generation by mitochondria respiratory complexes is a major source of reactive oxygen species (ROS) which are capable of initiating redox signalling and oxidative damage. Current understanding of the role of mitochondrial ROS in health and disease has been limited by the lack of experimental strategies to selectively induce mitochondrial superoxide production. The recently-developed mitochondria-targeted redox cycler MitoParaquat (MitoPQ) overcomes this limitation, and has proven effective in vitro and in Drosophila...
October 30, 2018: Free Radical Biology & Medicine
Zsolt Radak, Ferenc Torma, Istvan Berkes, Sataro Goto, Tatsuya Mimura, Aniko Posa, Laszlo Balogh, Istvan Boldogh, Katsuhiko Suzuki, Mitsuru Higuchi, Erika Koltai
The decrease in cognitive/motor functions and physical abilities severely affects the aging population in carrying out daily activities. These disabilities become a burden on individuals, families and society in general. It is known that aging conditions are ameliorated with regular exercise, which attenuates the age-associated decline in maximal oxygen uptake (VO2max), production of reactive oxygen species (ROS), decreases in oxidative damage to molecules, and functional impairment in various organs. While benefits of physical exercise are well-documented, the molecular mechanisms responsible for functional improvement and increases in health span are not well understood...
October 30, 2018: Free Radical Biology & Medicine
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