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https://www.readbyqxmd.com/read/30341612/induction-of-cu-zn-superoxide-dismutase-sod1-aggregation-in-living-cells
#1
Edward Pokrishevsky, Jeremy Nan, Neil R Cashman
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration and loss of motor neurons that appears to spread through the neuroaxis in a spatiotemporally restricted manner. In the familial form of ALS, the presence of any one of over 180 inherited mutations in the gene that encodes Cu/Zn superoxide dismutase (SOD1) leads to its eventual misfolding and aggregation. Once the pathological SOD1 seed is formed, it can continue growing into a larger aggregate through nucleation of other SOD1 substrate molecules...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30341605/high-throughput-microplate-based-fluorescence-assays-for-studying-stochastic-aggregation-of-superoxide-dismutase-1
#2
Alireza Abdolvahabi, Sanaz Rasouli, Corbin M Croom, Devon L Plewman
Investigating in vitro kinetics of superoxide dismutase-1 (SOD1) aggregation with high-throughput microplate-based assays provides valuable information regarding SOD1 pathogenesis in amyotrophic lateral sclerosis (ALS) and opens venues for the development of effective therapies. In this chapter, we first explain the step-by-step purification and demetallation of wild-type (WT) and ALS-variant SOD1 proteins from Saccharomyces cerevisiae (baker's yeast). We then describe the methodology for a microplate-based fluorescence assay that is used to study real-time kinetics of metal-free (apo)-SOD1 aggregation...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30341600/biophysical-and-spectroscopic-methods-for-monitoring-protein-misfolding-and-amyloid-aggregation
#3
Joana S Cristóvão, Bárbara J Henriques, Cláudio M Gomes
Proteins exhibit a remarkable structural plasticity and may undergo conformational changes resulting in protein misfolding both in a biological context and upon perturbing physiopathological conditions. Such nonfunctional protein conformers, including misfolded states and aggregates, are often associated to protein folding diseases. Understanding the biology of protein folding diseases thus requires tools that allow the structural characterization of nonnative conformations of proteins and their interconversions...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30328005/exposure-of-solvent-inaccessible-regions-in-the-amyloidogenic-protein-human-sod1-determined-by-hydroxyl-radical-footprinting
#4
Yuewei Sheng, Joseph Capri, Alan Waring, Joan Selverstone Valentine, Julian Whitelegge
Solvent-accessibility change plays a critical role in protein misfolding and aggregation, the culprit for several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mass spectrometry-based hydroxyl radical (·OH) protein footprinting has evolved as a powerful and fast tool in elucidating protein solvent accessibility. In this work, we used fast photochemical oxidation of protein (FPOP) hydroxyl radical (·OH) footprinting to investigate solvent accessibility in human copper-zinc superoxide dismutase (SOD1), misfolded or aggregated forms of which underlie a portion of ALS cases...
October 16, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/30326626/tissue-specific-profiling-of-oxidative-stress-associated-transcriptome-in-a-healthy-mouse-model
#5
Jung Min Kim, Hyeong Geug Kim, Chang Gue Son
Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes including aging. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability especially to age-related and chronic diseases. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions...
October 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30323744/reduced-excitability-and-increased-neurite-complexity-of-cortical-interneurons-in-a-familial-mouse-model-of-amyotrophic-lateral-sclerosis
#6
Rosemary M Clark, Mariana Brizuela, Catherine A Blizzard, Tracey C Dickson
Cortical interneurons play a crucial role in regulating inhibitory-excitatory balance in brain circuits, filtering synaptic information and dictating the activity of pyramidal cells through the release of GABA. In the fatal motor neuron (MN) disease, amyotrophic lateral sclerosis (ALS), an imbalance between excitation and inhibition is an early event in the motor cortex, preceding the development of overt clinical symptoms. Patients with both sporadic and familial forms of the disease exhibit reduced cortical inhibition, including patients with mutations in the copper/zinc superoxide-dismutase-1 (SOD1) gene...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/30323591/promoting-vascular-healing-using-nanofibrous-ticagrelor-eluting-stents
#7
Cheng-Hung Lee, Ming-Jer Hsieh, Kuo-Sheng Liu, Che-Wei Cheng, Shang-Hung Chang, Shih-Jung Liu, Chao-Jan Wang, Ming-Yi Hsu, Kuo-Chun Hung, Yung-Hsin Yeh, Wei-Jan Chen, I-Chang Hsieh, Jyuhn-Huarng Juang, Ming-Shien Wen
Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction. Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30321575/beclin1-decreases-the-ripa-insoluble-fraction-of-amyotrophic-lateral-sclerosis-linked-sod1-mutant-via-autophagy
#8
Yan-Ming Wei, Bo Han
Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterised by the intracellular appearance of protein aggregates or insoluble materials. Accelerated removal of related toxic proteins might be beneficial for these diseases. Here we describe an inducible role of Beclin1, an essential regulator for autophagy, in degradation of the familial ALS-linked Cu/Zn superoxide dismutase 1 (SOD1) mutant. We confirmed that the SOD1 mutant exhibited an increased RIPA (radioimmune precipitation assay buffer, containing NP40 and sodium deoxycholate)-insolubility compared with SOD1 wild-type (WT)...
October 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/30321544/protective-effects-of-sod2-overexpression-in-human-umbilical-cord-mesenchymal-stem-cells-on-lung-injury-induced-by-acute-paraquat-poisoning-in-rats
#9
Li-Chun Zhang, Yu Wang, Wei Liu, Xue-Min Zhang, Miao Fan, Min Zhao
AIMS: To study the protective effects and mechanisms of human umbilical cord mesenchymal stem cells (hUCMSCs) and overexpression of antioxidant gene SOD2 on lung injury by establishing a rat model of paraquat (PQ)-induced lung injury. MAIN METHODS: The hUCMSCs cell line overexpressed SOD2 was established. After intraperitoneal injection of PQ solution (24 mg/kg) 3 h later, the different groups of hUCMSCs cell lines were injected through the tail veins of rats...
October 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/30319424/luteolin-prevents-cardiometabolic-alterations-and-vascular-dysfunction-in-mice-with-hfd-induced-obesity
#10
Daniela Gentile, Matteo Fornai, Carolina Pellegrini, Rocchina Colucci, Laura Benvenuti, Emiliano Duranti, Stefano Masi, Sara Carpi, Paola Nieri, Anna Nericcio, Francesca Garelli, Agostino Virdis, Laura Pistelli, Corrado Blandizzi, Luca Antonioli
Purpose: Luteolin exerts beneficial effects against obesity-associated comorbidities, although its influence on vascular dysfunction remains undetermined. We examined the effects of luteolin on endothelial dysfunction in a mouse model of diet-induced obesity. Methods: Standard diet (SD) or high-fat diet (HFD)-fed mice were treated daily with luteolin intragastrically. After 8 weeks, body and epididymal fat weight, as well as blood cholesterol, glucose, and triglycerides were evaluated. Endothelium-dependent relaxations of resistance mesenteric vessels was assessed by a concentration-response curve to acetylcholine, repeated upon Nw -nitro-L-arginine methylester (L-NAME) or ascorbic acid infusion to investigate the influence of nitric oxide (NO) availability and reactive oxygen species (ROS) on endothelial function, respectively...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30317490/als-and-charge-syndrome-a-clinical-and-genetic-study
#11
Carmine Ungaro, Luigi Citrigno, Francesca Trojsi, Teresa Sprovieri, Giulia Gentile, Maria Muglia, Maria Rosaria Monsurrò, Gioacchino Tedeschi, Sebastiano Cavallaro, Francesca Luisa Conforti
Amyotrophic Lateral Sclerosis and CHARGE syndrome are complex neurological disorders, which never occurred together in the same family and, to date, no putative correlation between them has been described on PubMed Central. Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic description of two sisters affected by these two different disorders. In the CHARGE patient, molecular analysis of the CHD7 gene revealed the c.8016G >A de novo variant in exon 37...
October 13, 2018: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/30316201/the-copper-zinc-superoxide-dismutase-activity-in-selected-diseases
#12
REVIEW
Łukasz Lewandowski, Marta Kepinska, Halina Milnerowicz
Copper-zinc superoxide dismutase (Cu,Zn-SOD) plays a protective role in various types of tissue protecting them from oxidative damage. Alterations in copper-zinc superoxide dismutase (SOD1 and SOD3) activity and its expression has been observed in pathological occurrences most prevalent in modern society, including: inflammatory bowel disease, obesity and its implications - diabetes and hypertension, and chronic obstructive pulmonary disease. Moreover, several SOD1 and SOD3 gene polymorphisms have been associated with the risk of developing a particular type of disease, or its exacerbation...
October 13, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30315929/microglial-overexpression-of-fals-linked-mutant-sod1-induces-sod1-processing-impairment-activation-and-neurotoxicity-and-is-counteracted-by-the-autophagy-inducer-trehalose
#13
Francesca Massenzio, Emiliano Peña-Altamira, Sabrina Petralla, Marco Virgili, Giampaolo Zuccheri, Andrea Miti, Elisabetta Polazzi, Ilaria Mengoni, Deborah Piffaretti, Barbara Monti
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Mutations in the gene encoding copper/zinc superoxide dismutase-1 (SOD1) are responsible for most familiar cases, but the role of mutant SOD1 protein dysfunction in non-cell autonomous neurodegeneration, especially in relation to microglial activation, is still unclear. Here, we focused our study on microglial cells, which release SOD1 also through exosomes. We observed that in rat primary microglia the overexpression of the most-common SOD1 mutations linked to fALS (G93A and A4V) leads to SOD1 intracellular accumulation, which correlates to autophagy dysfunction and microglial activation...
October 10, 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30315444/oxidant-stress-induction-and-signalling-in-xenografted-human-breast-cancer-tissues-plus-estradiol-treated-or-n-ethyl-n-nitrosourea-treated-female-rats-via-altered-estrogen-sulfotransferase-rsult1e1-expressions-and-sod1-catalase-regulations
#14
Aarifa Nazmeen, Smarajit Maiti
N-ethyl-N-nitrosourea (ENU) is highly used in rodent models of tumerogenesis/carcinogenesis. Xenografting human-cancer tissues/cells with estradiol (E2) treatment is also used to generate rodent-models of gynaecological cancers. The altered metabolic-redox environment leading to establishment of pre-tumorigenesis condition and their mechanism are less studied. Here, female Wister rats were treated with these drugs at their pre-tumerogenic dosage (one group ENU single intra-peritoneal dose of 90 mg/kg b.w. and another group were implanted with human breast tumor (stage-IIIB) and fed with 2...
October 12, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/30312797/fisetin-inhibits-cardiac-hypertrophy-by-suppressing-oxidative-stress
#15
Bin Dong, Chen Liu, Ruicong Xue, Yan Wang, Yu Sun, Zhuomin Liang, Wendong Fan, Jingzhou Jiang, Jingjing Zhao, Qiao Su, Gang Dai, Yugang Dong, Huiling Huang
Cardiac hypertrophy is a pathophysiological response to various pathological stresses and ultimately leads to heart failure. Oxidative stress is one of the critical processes involved in hypertrophy development. Fisetin, a small molecular flavonoid, has been shown to have anti-oxidative, anti-proliferative and anti-inflammatory properties. However, the effect of fisetin on cardiac hypertrophy remains unknown. In our present study, we showed that fisetin inhibited pressure overload-induced cardiac hypertrophy, improved cardiac function in vivo and suppressed phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro...
September 1, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/30311784/molecular-investigation-to-rna-and-protein-based-interaction-induced-in-vivo-biocompatibility-of-phytofabricated-aunp-with-embryonic-zebrafish
#16
Suresh K Verma, Ealisha Jha, Pritam Kumar Panda, Puja Kumari, Nandini Pramanik, Shalini Kumari, Arun Thirumurugan
Implication of gold nanoparticles in industrial and day-to-day life products at extensive scale has raised concern about their toxicity to environment and human health. Moreover, quest of new technologies for production of biocompatible nanoparticles increased. This study explores the molecular toxicology of AuNP with enlightenment of their green synthesis using medicinal plant extract as reducing and stabilizing agent. Synthesized CAuNP were characterized for their physiochemical properties by standard techniques like FESEM, TEM, DLS, UV-Vis spectroscopy and FTIR...
October 12, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/30310673/molecular-insight-to-size-and-dose-dependent-cellular-toxicity-exhibited-by-a-green-synthesized-bioceramic-nanohybrid-with-macrophages-for-dental-applications
#17
Hardik Makkar, Suresh K Verma, Pritam Kumar Panda, Nandini Pramanik, Ealisha Jha, Mrutyunjay Suar
Improvising bioceramics for enhancing their biocompatibility and physical properties has been a focus area for the dental industry. To further explore this area, this study reports a novel green synthesis and molecular in vitro biocompatibility of calcium aluminosilicate-chitosan nanohybrid (CAS-CH). The nanohybrids were synthesized by using a high energy ball milling (HEBM) technique and then characterized for their physiochemical properties using standard techniques including scanning electron microscopy (SEM) and dynamic light scattering (DLS)...
September 1, 2018: Toxicology Research
https://www.readbyqxmd.com/read/30310662/oxidative-stress-and-mitochondrial-impairment-mediated-apoptotic-cell-death-induced-by-terpinolene-in-schizosaccharomyces-pombe
#18
Hizlan H Agus, Cemaynur Sarp, Meryem Cemiloglu
Terpinolene is one of the most abundant monoterpenes used as a food supplement or odorant in cosmetics and the pharmaceutical industry. In this study, we aimed to assess apoptotic, oxidative and cytotoxic effects of terpinolene. We used the fission yeast ( Schizosaccharomyces pombe ) as a promising uni-cellular model organism in molecular toxicology and cell death research, due to its resemblance to mammalian cells at the molecular level. After terpinolene exposure (200-800 mg L-1 ), the IC50 and LC50 were calculated as 349...
September 1, 2018: Toxicology Research
https://www.readbyqxmd.com/read/30300572/motor-neuron-abnormalities-correlate-with-impaired-movement-in-zebrafish-that-express-mutant-superoxide-dismutase-1
#19
Katherine J Robinson, Kristy C Yuan, Emily K Don, Alison L Hogan, Claire G Winnick, Madelaine C Tym, Caitlin W Lucas, Hamideh Shahheydari, Maxinne Watchon, Ian P Blair, Julie D Atkin, Garth A Nicholson, Nicholas J Cole, Angela S Laird
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. ALS can be modeled in zebrafish (Danio rerio) through the expression of human ALS-causing genes, such as superoxide dismutase 1 (SOD1). Overexpression of mutated human SOD1 protein causes aberrant branching and shortening of spinal motor axons. Despite this, the functional relevance of this axon morphology remains elusive. Our aim was to determine whether this motor axonopathy is correlated with impaired movement in mutant (MT) SOD1-expressing zebrafish...
October 9, 2018: Zebrafish
https://www.readbyqxmd.com/read/30296699/restoration-of-serca-atpase-prevents-oxidative-stress-related-muscle-atrophy-and-weakness
#20
Rizwan Qaisar, Shylesh Bhaskaran, Rojina Ranjit, Kavithalakshmi Sataranatarajan, Pavithra Premkumar, Kendra Huseman, Holly Van Remmen
Molecular targets to reduce muscle weakness and atrophy due to oxidative stress have been elusive. Here we show that activation of Sarcoplasmic Reticulum (SR) Ca2+ ATPase (SERCA) with CDN1163, a novel small molecule allosteric SERCA activator, ameliorates the muscle impairment in the CuZnSOD deficient (Sod1-/- ) mouse model of oxidative stress. Sod1-/- mice are characterized by reduced SERCA activity, muscle weakness and atrophy, increased oxidative stress and mitochondrial dysfunction. Seven weeks of CDN1163 treatment completely restored SERCA activity and reversed the 23% reduction in gastrocnemius mass and 22% reduction in specific force in untreated Sod1-/- versus wild type mice...
September 27, 2018: Redox Biology
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