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Redox Biology

Juan de Dios Alché
Polyunsaturated fatty acids present in plant membranes react with reactive oxygen species through so-called lipid oxidation events. They generate great diversity of highly-reactive lipid-derived chemical species, which may be further degraded enzymatically or non-enzymatically originating new components like Reactive Carbonyl Species (RCS). Such RCS are able to selectively react with proteins frequently producing loss of function through lipoxidation reactions. Although a basal concentration of lipoxidation products exists in plants (likely involved in signaling), their concentration and variability growth exponentially when plants are subjected to biotic/abiotic stresses...
February 7, 2019: Redox Biology
Wen Wu, Wei Zhang, Mihyun Choi, Jinjing Zhao, Ping Gao, Min Xue, Harold A Singer, David Jourd'heuil, Xiaochun Long
Injury-induced stenosis is a serious vascular complication. We previously reported that p38α (MAPK14), a redox-regulated p38MAPK family member was a negative regulator of the VSMC contractile phenotype in vitro. Here we evaluated the function of VSMC-MAPK14 in vivo in injury-induced neointima hyperplasia and the underlying mechanism using an inducible SMC-MAPK14 knockout mouse line (iSMC-MAPK14-/- ). We show that MAPK14 expression and activity were induced in VSMCs after carotid artery ligation injury in mice and ex vivo cultured human saphenous veins...
February 6, 2019: Redox Biology
Sara Castro-Sánchez, Ángel J García-Yagüe, Sebastian Kügler, Isabel Lastres-Becker
TAU protein aggregation is the main characteristic of neurodegenerative diseases known as tauopathies. Low-grade chronic inflammation is also another hallmark that indicates crosstalk between damaged neurons and glial cells. Previously, we have demonstrated that neurons overexpressing TAUP301L release CX3CL1, which activates the transcription factor NRF2 signalling to limit over-activation in microglial cells in vitro and in vivo. However, the connection between CX3CL1/CX3CR1 and NRF2 system and its functional implications in microglia are poorly described...
February 6, 2019: Redox Biology
Jiahao Zhang, Huachao Li, Qipeng Wu, Yueming Chen, Yanchao Deng, Zhicheng Yang, Luyong Zhang, Bing Liu
M2-type tumor-associated macrophages (TAMs) infiltration contributes to cancer malignant progression. However, the mechanisms for controlling recruitment and M2 polarization of macrophages by cancer cells are largely unclear. NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and mediates cancer progression. NOXs are in close relation with cancer-related inflammation, nevertheless, whether tumoral NOXs influence microenvironmental macrophages remains undentified. This study found that there was a close association between NOX4 expression and macrophage chemotaxis in patients with NSCLC analyzed using TCGA RNA-sequencing data...
February 6, 2019: Redox Biology
Anita Carija, Francisca Pinheiro, Jordi Pujols, Inês C Brás, Diana Fernandes Lázaro, Carlo Santambrogio, Rita Grandori, Tiago F Outeiro, Susanna Navarro, Salvador Ventura
The aggregation of α-synuclein (α-syn) into amyloid fibrils is a major pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. The mechanisms underlying the structural transition of soluble and innocuous α-syn to aggregated neurotoxic forms remains largely unknown. The disordered nature of α-syn has hampered the use of structure-based protein engineering approaches to elucidate the molecular determinants of this transition. The recent 3D structure of a pathogenic α-syn fibril provides a template for this kind of studies...
February 5, 2019: Redox Biology
Nicholas K H Khoo, Marco Fazzari, Dionysios V Chartoumpekis, Lihua Li, Danielle Aparecida Guimaraes, Gavin E Arteel, Sruti Shiva, Bruce A Freeman
Non-alcoholic fatty liver disease (NAFLD) is linked to obesity and insulin resistance and is the most prevalent chronic liver disease. During the development of obesity and NAFLD, mitochondria adapt to the increased lipid load in hepatocytes by increasing the rate of fatty acid oxidation. In concert with this, reactive species (RS) generation is increased, damaging hepatocytes and inducing inflammation. Hepatic mitochondrial dysfunction is central to the pathogenesis of NAFLD via undefined mechanisms. There are no FDA approved treatments for NAFLD other than weight loss and management of glucose tolerance...
February 1, 2019: Redox Biology
Sandra I Anjo, Matilde N Melo, Liliana R Loureiro, Lúcia Sabala, Pedro Castanheira, Mário Grãos, Bruno Manadas
Most of the redox proteomics strategies are focused on the identification and relative quantification of cysteine oxidation without considering the variation in the total levels of the proteins. However, protein synthesis and protein degradation also belong to the regulatory mechanisms of the cells, being therefore important to consider the changes in total protein levels in PTMs-focused analyses, such as cysteine redox characterization. Therefore, a novel integrative approach combining the SWATH-MS method with differential alkylation using a combination of commonly available alkylating reagents (oxSWATH) is presented, by which it is possible to integrate the information regarding relative cysteine oxidation with the analysis of the total protein levels in a cost-effective high-throughput approach...
January 30, 2019: Redox Biology
Yunjiang Zhou, Yang Zhou, Mengdi Yang, Keke Wang, Yisi Liu, Mingda Zhang, Yunjia Yang, Chenyu Jin, Rui Wang, Rong Hu
Chemoresistance is a major therapeutic obstacle in the treatment of human pancreatic ductal adenocarcinoma (PDAC). As an oxidative stress responsive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of cytoprotective genes. Nrf2 not only plays a critical role in chemoprevention, but also contributes to chemoresistance. In this study, we found that digoxin markedly reversed drug resistance of gemcitabine by inhibiting Nrf2 signaling in SW1990/Gem and Panc-1/Gem cells...
January 30, 2019: Redox Biology
Alejandro Gonzalez-Candia, Marcelino Veliz, Catalina Carrasco-Pozo, Rodrigo L Castillo, J Cesar Cárdenas, Germán Ebensperger, Roberto V Reyes, Aníbal J Llanos, Emilio A Herrera
Chronic hypobaric hypoxia during fetal and neonatal life induces neonatal pulmonary hypertension. Hypoxia and oxidative stress are driving this condition, which implies an increase generation of reactive oxygen species (ROS) and/or decreased antioxidant capacity. Melatonin has antioxidant properties that decrease oxidative stress and improves pulmonary vascular function when administered postnatally. However, the effects of an antenatal treatment with melatonin in the neonatal pulmonary function and oxidative status are unknown...
January 29, 2019: Redox Biology
Nicolas Chamberlain, Bethany R Korwin-Mihavics, Emily M Nakada, Sierra R Bruno, David E Heppner, David G Chapman, Sidra M Hoffman, Albert van der Vliet, Benjamin T Suratt, Oliver Dienz, John F Alcorn, Vikas Anathy
Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection...
January 29, 2019: Redox Biology
Oliver Löwe, Flávia Rezende, Juliana Heidler, Ilka Wittig, Valeska Helfinger, Ralf P Brandes, Katrin Schröder
AIM: NADPH oxidase (Nox) -derived reactive oxygen species have been implicated in redox signaling via cysteine oxidation in target proteins. Although the importance of oxidation of target proteins is well known, the specificity of such events is often debated. Only a limited number of Nox-oxidized proteins have been identified thus far; especially little is known concerning redox-targets of the constitutively active NADPH oxidase Nox4. In this study, HEK293 cells with tetracycline-inducible Nox4 overexpression (HEK-tet-Nox4), as well as podocytes of WT and Nox4-/- mice, were utilized to identify Nox4-dependent redox-modified proteins...
January 29, 2019: Redox Biology
I Pradas, M Jové, K Huynh, J Puig, M Ingles, C Borras, J Viña, P J Meikle, R Pamplona
A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state...
January 29, 2019: Redox Biology
Paul Guerby, Audrey Swiader, Nathalie Augé, Olivier Parant, Christophe Vayssière, Koji Uchida, Robert Salvayre, Anne Negre-Salvayre
Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2 •- ). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies...
January 26, 2019: Redox Biology
Ludivine Doridot, Mohamed Jeljeli, Charlotte Chêne, Frédéric Batteux
Systemic sclerosis is an autoimmune disorder characterized by inflammation and a progressive fibrosis affecting the skin and visceral organs. Over the last two decades, it became clear that oxidative stress plays a key role in its pathogenesis. In this review, we highlighted the role of ROS in the various pathological components of systemic sclerosis, namely the inflammatory, the autoimmune and the fibrotic processes. We also discussed how these pathological processes can induce ROS overproduction, thus maintaining a vicious circle...
January 25, 2019: Redox Biology
Ananya Pal, Hsin Yao Chiu, Reshma Taneja
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma accounting for 5-8% of malignant tumours in children and adolescents. Children with high risk disease have poor prognosis. Anti-RMS therapies include surgery, radiation and combination chemotherapy. While these strategies improved survival rates, they have plateaued since 1990s as drugs that target differentiation and self-renewal of tumours cells have not been identified. Moreover, prevailing treatments are aggressive with drug resistance and metastasis causing failure of several treatment regimes...
January 25, 2019: Redox Biology
Giulia Coliva, Sofia Duarte, Dolores Pérez-Sala, Maria Fedorova
Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins and even organelles. Biomolecules carbonylation, an irreversible oxidative modification, occurs in a variety of pathological conditions and is generally viewed as a marker of oxidative stress. Here, we used a model of rat primary cardiac cells to elucidate the role of autophagy-lysosomal pathway in the turnover of carbonylated biomolecules...
January 24, 2019: Redox Biology
Tao Zhou, Ling Chang, Yi Luo, Ying Zhou, Jianjun Zhang
Obesity-related non-alcoholic fatty liver disease (NAFLD) is connected with mitochondrial stress and hepatocyte apoptosis. Parkin-related mitophagy sustains mitochondrial homeostasis and hepatocyte viability. However, the contribution and regulatory mechanisms of Parkin-related mitophagy in NAFLD are incompletely understood. Macrophage stimulating 1 (Mst1) is a novel mitophagy upstream regulator which excerbates heart and cancer apoptosisn via repressing mitophagy activity. The aim of our study is to explore whether Mst1 contributes to NAFLD via disrupting Parkin-related mitophagy...
January 23, 2019: Redox Biology
Jianhua Peng, Jinwei Pang, Lei Huang, Budbazar Enkhjargal, Tongyu Zhang, Jun Mo, Pei Wu, Weilin Xu, Yuchun Zuo, Jun Peng, Gang Zuo, Ligang Chen, Jiping Tang, John H Zhang, Yong Jiang
White matter injury (WMI) is associated with motor deficits and cognitive dysfunctions in subarachnoid hemorrhage (SAH) patients. Therapeutic strategy targeting WMI would likely improve the neurological outcomes after SAH. Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor of apolipoprotein E (apoE), is able to modulate microglia polarization towards anti-inflammatory M2 phenotypes during inflammatory and oxidative insult. In the present study, we investigated the effects of LRP1 activation on WMI and underlying mechanisms of M2 microglial polarization in a rat model of SAH...
January 23, 2019: Redox Biology
Andrew F Cumpstey, Magdalena Minnion, Bernadette O Fernandez, Monika Mikus-Lelinska, Kay Mitchell, Daniel S Martin, Michael P W Grocott, Martin Feelisch
The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this 'Reactive Species Interactome' (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges...
January 22, 2019: Redox Biology
Tommi Patinen, Simone Adinolfi, Carlos Cruz Cortés, Jouni Härkönen, Ashik Jawahar Deen, Anna-Liisa Levonen
Enzymatic and non-enzymatic oxidation of unsaturated fatty acids gives rise to reactive species that covalently modify nucleophilic residues within redox sensitive protein sensors in a process called lipoxidation. This triggers adaptive signaling pathways that ultimately lead to increased resistance to stress. In this graphical review, we will provide an overview of pathways affected by protein lipoxidation and the key signaling proteins being altered, focusing on the KEAP1-NRF2 and heat shock response pathways...
January 16, 2019: Redox Biology
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