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Redox Biology

Seila Fernandez-Fernandez, Veronica Bobo-Jimenez, Raquel Requejo-Aguilar, Silvia Gonzalez-Fernandez, Monica Resch, Monica Carabias-Carrasco, Joaquim Ros, Angeles Almeida, Juan P Bolaños
Loss of brain glutathione has been associated with cognitive decline and neuronal death during aging and neurodegenerative diseases. However, whether decreased glutathione precedes or follows neuronal dysfunction has not been unambiguously elucidated. Previous attempts to address this issue were approached by fully eliminating glutathione, a strategy causing abrupt lethality or premature neuronal death that led to multiple interpretations. To overcome this drawback, here we aimed to moderately decrease glutathione content by genetically knocking down the rate-limiting enzyme of glutathione biosynthesis in mouse neurons in vivo...
August 7, 2018: Redox Biology
Erika Koltai, Zoltan Bori, Peter Osvath, Ferenc Ihasz, Szablics Peter, Geza Toth, Hans Degens, Jörn Rittweger, Istvan Boldogh, Zsolt Radak
Regular physical exercise has health benefits and can prevent some of the ageing-associated muscle deteriorations. However, the biochemical mechanisms underlying this exercise benefit, especially in human tissues, are not well known. To investigate, we assessed this using miRNA profiling, mRNA and protein levels of anti-oxidant and metabolic proteins in the vastus lateralis muscle of master athletes aged over 65 years and age-matched controls. Master athletes had lower levels of miR-7, while mRNA or protein levels of SIRT3, SIRT1, SOD2, and FOXO1 levels were significantly higher in the vastus lateralis muscle of master athletes compared to muscles of age-matched controls...
August 7, 2018: Redox Biology
Andrea Irías-Mata, Nadine Sus, Sandra Flory, Daniela Stock, Denise Woerner, Maren Podszun, Jan Frank
Liver cells express a cytosolic α-tocopherol transfer protein (αTTP) with high binding affinity for α-tocopherol (αT) and much lower affinities for the non-αT congeners. The role of αTTP in the intracellular distribution of the different vitamin E forms is currently unknown. We therefore investigated the intracellular localization of αT, γ-tocopherol (γT), α-tocotrienol (αT3), and γ-tocotrienol (γT3) in cultured hepatic cells with and without stable expression of αTTP. We first determined cellular uptake of the four congeners and found the methylation of the chromanol ring and saturation of the sidechain to be important factors, with tocotrienols being taken up more efficiently than tocopherols and the γ-congeners more than the α-congeners, irrespective of the expression of αTTP...
August 5, 2018: Redox Biology
Svetlana Konovalova, Xiaonan Liu, Pooja Manjunath, Sundar Baral, Nirajan Neupane, Taru Hilander, Yang Yang, Diego Balboa, Mügen Terzioglu, Liliya Euro, Markku Varjosalo, Henna Tyynismaa
Mitochondria are central organelles to cellular metabolism. Their function relies largely on nuclear-encoded proteins that must be imported from the cytosol, and thus the protein import pathways are important for the maintenance of mitochondrial proteostasis. Mitochondrial HSP70 (mtHsp70) is a key component in facilitating the translocation of proteins through the inner membrane into the mitochondrial matrix. Its protein folding cycle is regulated by the nucleotide-exchange factor GrpE, which triggers the release of folded proteins by ATP rebinding...
August 4, 2018: Redox Biology
Stephanie E Oh, Hye-Jin Park, Liqiang He, Catherine Skibiel, Eunsung Junn, M Maral Mouradian
DJ-1 is a highly conserved protein that protects neurons against oxidative stress and whose loss of function mutations are linked to recessively inherited Parkinson's disease (PD). While a number of signaling pathways have been shown to be regulated by DJ-1, its role in controlling cell survival through non-coding RNAs remains poorly understood. Here, using a microarray screen, we found that knocking down DJ-1 in human neuroblastoma cells results in down-regulation of microRNA-221 (miR-221). This is one of the most abundant miRNAs in the human brain and promotes neurite outgrowth and neuronal differentiation...
August 3, 2018: Redox Biology
Priya K Prasai, Bandana Shrestha, A Wayne Orr, Christopher B Pattillo
The angiogenic capacity of local tissue critically regulates the response to ischemic injury. Elevated reactive oxygen species production, commonly associated with ischemic injury, has been shown to promote phosphorylation of the vascular endothelial growth factor receptor 2 (VEGFR2), a critical regulator of angiogenesis. Previous data from our lab demonstrated that diminished levels of the antioxidant glutathione positively augment ischemic angiogenesis. Here, we sought to determine the relationship between glutathione levels and oxidative stress in VEGFR2 signaling...
July 25, 2018: Redox Biology
Joey De Backer, Jamoliddin Razzokov, Dietmar Hammerschmid, Carl Mensch, Zainab Hafideddine, Naresh Kumar, Geert van Raemdonck, Maksudbek Yusupov, Sabine Van Doorslaer, Christian Johannessen, Frank Sobott, Annemie Bogaerts, Sylvia Dewilde
Many current anti-cancer therapies rely on increasing the intracellular reactive oxygen and nitrogen species (RONS) contents with the aim to induce irreparable damage, which subsequently results in tumor cell death. A novel tool in cancer therapy is the use of cold atmospheric plasma (CAP), which has been found to be very effective in the treatment of many different cancer cell types in vitro as well as in vivo, mainly through the vast generation of RONS. One of the key determinants of the cell's fate will be the interaction of RONS, generated by CAP, with important proteins, i...
July 24, 2018: Redox Biology
Shanshan Zhou, Jiqun Wang, Xia Yin, Ying Xin, Zhiguo Zhang, Taixing Cui, Jun Cai, Yang Zheng, Quan Liu, Lu Cai
We reported previously that nuclear factor erythroid 2-related factor 2 (Nrf2) and metallothionein (MT) play critical roles in preventing intermittent hypoxia (IH)-induced cardiomyopathy. In addition, positive feedback regulation between Nrf2 and MT is required for the efficient compensative responses of the heart to IH. As an activator of Nrf2, sulforaphane (SFN) has attracted attention as a potential protective agent against cardiovascular disease. Here, we investigated whether SFN can up-regulate cardiac Nrf2 expression and function, as well as MT expression, to prevent IH-induced cardiomyopathy, and if so, whether Nrf2 and MT are indispensable for this preventive effect...
July 21, 2018: Redox Biology
Sofia-Iris Bibli, Bert Luck, Sven Zukunft, Janina Wittig, Wei Chen, Ming Xian, Andreas Papapetropoulos, Jiong Hu, Ingrid Fleming
Hydrogen sulfide (H2 S) is a gasotransmitter that regulates cellular homeostasis and impacts on multiple physiological and pathophysiological processes. However, it exerts many of its biological actions indirectly via the formation of H2 S-derived sulfane sulfur species/polysulfides. Because of the high reactivity of sulfur species, the detection of H2 S-derived polysulfides in biological systems is challenging and currently used methods are neither sensitive nor quantitative. Herein, we describe a LC-MS/MS-based method that makes use of Sulfane Sulfur Probe 4 to detect endogenously generated polysulfides in biological samples in a selective, sensitive and quantitative manner...
July 21, 2018: Redox Biology
Claudia Jara, Alejandra Aránguiz, Waldo Cerpa, Cheril Tapia-Rojas, Rodrigo A Quintanilla
Tau is a key protein for microtubule stability; however, post-translationally modified tau contributes to neurodegenerative diseases by forming tau aggregates in the neurons. Previous reports from our group and others have shown that pathological forms of tau are toxic and impair mitochondrial function, whereas tau deletion is neuroprotective. However, the effects of tau ablation on brain structure and function in young mice have not been fully elucidated. Therefore, the aim of this study was to investigate the implications of tau ablation on the mitochondrial function and cognitive abilities of a litter of young mice (3 months old)...
July 19, 2018: Redox Biology
Yuan Liu, Li-Na Li, Sen Guo, Xiao-Yan Zhao, Yu-Zhou Liu, Cui Liang, Sheng Tu, Dan Wang, Ling Li, Jian-Zeng Dong, Lu Gao, Hai-Bo Yang
Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD...
July 11, 2018: Redox Biology
Ana I Rojo, Marta Pajares, Angel J García-Yagüe, Izaskun Buendia, Fred Van Leuven, Masayuki Yamamoto, Manuela G López, Antonio Cuadrado
Chronic neuroinflammation is a hallmark of the onset and progression of brain proteinopathies such as Alzheimer disease (AD) and it is suspected to participate in the neurodegenerative process. Transcription factor NRF2, a master regulator of redox homeostasis, controls acute inflammation but its relevance in low-grade chronic inflammation of AD is inconclusive due to lack of good mouse models. We have addressed this question in a transgenic mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency (AT-NRF2-KO)...
July 11, 2018: Redox Biology
Alejandro F Prado, Laena Pernomian, Aline Azevedo, Rute A P Costa, Elen Rizzi, Junia Ramos, Adriana F Paes Leme, Lusiane M Bendhack, Jose E Tanus-Santos, Raquel F Gerlach
Increased reactive oxygen species (ROS) formation may enhance matrix metalloproteinase (MMP)-2 activity and promote cardiovascular dysfunction. We show for the first time that MMP-2 is upstream of increased ROS formation and activates signaling mechanisms impairing redox balance. Incubation of vascular smooth muscle cells (VSMC) with recombinant MMP-2 increased ROS formation assessed with dihydroethidium (DHE) by flow cytometry. This effect was blocked by the antioxidant apocynin or by polyethylene glycol-catalase (PEG-catalase), and by MMP inhibitors (doxycycline or GM6001)...
July 9, 2018: Redox Biology
Pengfei Xu, Qian Liu, Yi Xie, Xiaolei Shi, Yunzi Li, Mengna Peng, Hongquan Guo, Rui Sun, Juanji Li, Ye Hong, Xinfeng Liu, Gelin Xu
Cellular oxidative stress plays a vital role in the pathological process of neural damage in cerebral ischemia/reperfusion (I/R). The breast cancer susceptibility protein 1 (BRCA1), a tumor suppressor, can modulate cellular antioxidant response and DNA repair. Yet the role of BRCA1 in cerebral I/R injury has not been explored. In this study, we observed that BRCA1 was mainly expressed in neurons and was up-regulated in response to I/R insult. Overexpression of BRCA1 attenuated reactive oxygen species production and lipid peroxidation...
July 7, 2018: Redox Biology
Ming Shen, Yan Cao, Yi Jiang, Yinghui Wei, Honglin Liu
Oxidative stress has been described as a prime driver of granulosa cell (GCs) death during follicular atresia. Increasing evidence suggests potential roles of melatonin in protecting GCs from oxidative injury, though the underlying mechanisms remain largely undetermined. Here we first proposed that the inhibition of autophagy through some novel regulators contributes to melatonin-mediated GCs survival under conditions of oxidative stress. Oxidant-induced loss of GCs viability was significantly reduced after melatonin administration, which was correlated with attenuated autophagic signals upon oxidative stimulation both in vivo and in vitro...
July 7, 2018: Redox Biology
María José Iglesias, María Cecilia Terrile, Natalia Correa-Aragunde, Silvana Lorena Colman, Alicia Izquierdo-Álvarez, Diego Fernando Fiol, Ramiro París, Nuria Sánchez-López, Anabel Marina, Luz Irina A Calderón Villalobos, Mark Estelle, Lorenzo Lamattina, Antonio Martínez-Ruiz, Claudia Anahí Casalongué
The F-box proteins (FBPs) TIR1/AFBs are the substrate recognition subunits of SKP1-cullin-F-box (SCF) ubiquitin ligase complexes and together with Aux/IAAs form the auxin co-receptor. Although tremendous knowledge on auxin perception and signaling has been gained in the last years, SCFTIR1/AFBs complex assembly and stabilization are emerging as new layers of regulation. Here, we investigated how nitric oxide (NO), through S-nitrosylation of ASK1 is involved in SCFTIR1/AFBs assembly. We demonstrate that ASK1 is S-nitrosylated and S-glutathionylated in cysteine (Cys) 37 and Cys118 residues in vitro...
July 6, 2018: Redox Biology
Xiao-Juan Zhao, Han-Wen Yu, Yan-Zi Yang, Wen-Yuan Wu, Tian-Yu Chen, Ke-Ke Jia, Lin-Lin Kang, Rui-Qing Jiao, Ling-Dong Kong
Oxidative stress is a critical factor in nonalcoholic fatty liver disease pathogenesis. MicroRNA-200a (miR-200a) is reported to target Kelch-like ECH-associated protein 1 (Keap1), which regulates nuclear factor erythroid 2-related factor 2 (Nrf2) anti-oxidant pathway. Polydatin (3,4',5-trihydroxy-stilbene-3-β-D-glucoside), a polyphenol found in the rhizome of Polygonum cuspidatum, have anti-oxidative, anti-inflammatory and anti-hyperlipidemic effects. However, whether miR-200a controls Keap1/Nrf2 pathway in fructose-induced liver inflammation and lipid deposition and the blockade of polydatin are still not clear...
July 5, 2018: Redox Biology
Yun Hee Kim, Seung-Hyo Lee
Elevated levels of mitochondrial reactive oxygen species (ROS) can lead to the development of airway inflammation. In this study, we investigated the role of Aspergillus proteases-which contribute to the pathogenesis of Aspergillus-induced diseases such as allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and atopic asthma-and their mechanisms of action in airway inflammation using primary human bronchial epithelial cells, and evaluated the inflammatory responses mediated by mitochondrial ROS...
July 5, 2018: Redox Biology
Chiang-Wen Lee, Cheng-Hsun Wu, Yao-Chang Chiang, Yuh-Lien Chen, Kuo-Ting Chang, Chu-Chun Chuang, I-Ta Lee
Pseudomonas aeruginosa (P. aeruginosa) infection in the lung is common in patients with cystic fibrosis (CF). Intercellular adhesion molecule-1 (ICAM-1) is known to play a key role in lung inflammation. Acute inflammation and its timely resolution are important to ensure bacterial clearance and limit tissue damage. Carbon monoxide (CO) has been shown to exert anti-inflammatory effects in various tissues and organ systems. Here, we explored the protective effects and mechanisms of carbon monoxide releasing molecule-2 (CORM-2) on P...
July 4, 2018: Redox Biology
Hannah M Southam, Thomas W Smith, Rhiannon L Lyon, Chunyan Liao, Clare R Trevitt, Laurence A Middlemiss, Francesca L Cox, Jonathan A Chapman, Sherif F El-Khamisy, Michael Hippler, Michael P Williamson, Peter J F Henderson, Robert K Poole
Carbon monoxide (CO)-releasing molecules (CORMs), mostly metal carbonyl compounds, are extensively used as experimental tools to deliver CO, a biological 'gasotransmitter', in mammalian systems. CORMs are also explored as potential novel antimicrobial drugs, effectively and rapidly killing bacteria in vitro and in animal models, but are reportedly benign towards mammalian cells. Ru-carbonyl CORMs, exemplified by CORM-3 (Ru(CO)3 Cl(glycinate)), exhibit the most potent antimicrobial effects against Escherichia coli...
June 30, 2018: Redox Biology
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