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SOD mimetic

Alice Biosa, Alvaro Sanchez-Martinez, Roberta Filograna, Ana Terriente-Felix, Sarah M Alam, Mariano Beltramini, Luigi Bubacco, Marco Bisaglia, Alexander J Whitworth
Reactive oxygen species exert important functions in regulating several cellular signalling pathways. However, an excessive accumulation of reactive oxygen species can perturb the redox homeostasis leading to oxidative stress, a condition which has been associated to many neurodegenerative disorders. Accordingly, alterations in the redox state of cells and mitochondrial homeostasis are established hallmarks in both familial and sporadic Parkinson's disease cases. PINK1 and parkin are two genes which account for a large fraction of autosomal recessive early-onset forms of Parkinson's disease and are now firmly associated to both mitochondria and redox homeostasis...
February 24, 2018: Human Molecular Genetics
Jihong Xing, Jian Lu, Jiahao Liu, Jianhua Li
The exercise pressor reflex is amplified in patients with peripheral artery disease (PAD) and in an experimental PAD model of rats induced by femoral artery occlusion. Heightened blood pressure worsens the restricted blood flow directed to the limbs in this disease. The purpose of this study was to determine the role played by muscle oxidative stress in regulating the augmented pressor response to static exercise in PAD. We hypothesized that limb ischemia impairs muscle superoxide dismutase (SOD) thereby leading to abnormal autonomic responsiveness observed in PAD animals, and a chronic compensation of SOD for anti-oxidation improves the exaggerated exercise pressor reflex...
2018: Frontiers in Physiology
Collin D Heer, Andrew B Davis, David B Riffe, Brett A Wagner, Kelly C Falls, Bryan G Allen, Garry R Buettner, Robert A Beardsley, Dennis P Riley, Douglas R Spitz
Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H₂O₂. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several cancer types...
January 19, 2018: Antioxidants (Basel, Switzerland)
Briana Ormsbee Golden, Brandon Griess, Shakeel Mir, Matthew Fitzgerald, Charlotte Kuperwasser, Frederick Domann, Melissa Teoh-Fitzgerald
We have previously shown tumor suppressive effects of extracellular superoxide dismutase, EcSOD in breast cancer cells. In this study, an RTK signaling array revealed an inhibitory effect of EcSOD on c-Met phosphorylation and its downstream kinase c-Abl in MDA-MB231 cells. Moreover, an extracellular protein array showed that thrombospondin 1 (TSP-1), a scavenger of the c-Met ligand, hepatocyte growth factor (HGF) is significantly up-regulated in EcSOD overexpressing cells (Ec.20). We further determined the effects of EcSOD on HGF/c-Met-mediated cancer-fibroblast interactions by co-culturing normal fibroblasts (RMF) or RMF which overexpresses HGF (RMF-HGF) with MDA-MB231 cells...
December 8, 2017: Oncotarget
Zachary P Zenner, Kevin L Gordish, William H Beierwaltes
We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium-hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure...
2018: Integrated Blood Pressure Control
Iram Musharaf, Martha Hinton, Man Yi, Shyamala Dakshinamurti
Infants with lung disease may be exposed to high O2 concentrations, and may have transient hypoxic episodes due to worsening lung pathophysiology, aggravating pulmonary arterial (PA) oxidative stress. NADPH oxidase (NOX) converts O2 to superoxide. Mitochondrial antioxidants such as superoxide dismutase (SOD) are sensitive to O2 tension. We previously reported decreased SOD2 activity in hypoxic PA myocytes due to nitration. In this study, we examined whether a transient hypoxic episode exposes antioxidant defense defects in hyperoxic PA myocytes...
December 12, 2017: Pulmonary Pharmacology & Therapeutics
Rosalin Bonetta
Natural as well as synthetic antioxidants are constantly being investigated for their efficiency in combatting the effects of oxidative stress, which appears to be the responsible cause of several diseases, which include cancer, central nervous system disorders, ischaemia-reperfusion disorders, cardiovascular conditions and diabetes. Superoxide dismutases (SODs) constitute the ubiquitous antioxidant defenses against oxidative stress that underlies numerous pathological conditions. Therefore, the development of therapeutics aimed at either delivering MnSOD more effectively to target tissues in the body in the form of MnSOD gene therapy, or the synthesis of molecules that mimic the activity of superoxide dismutase is constantly being explored...
November 12, 2017: Chemistry: a European Journal
Gina M Coudriet, Meghan M Delmastro-Greenwood, Dana M Previte, Meghan L Marré, Erin C O'Connor, Elizabeth A Novak, Garret Vincent, Kevin P Mollen, Sojin Lee, H Henry Dong, Jon D Piganelli
Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition and a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired insulin signaling leads to hyperglycemia and long-term complications, including metabolic liver dysfunction, resulting in non-alcoholic fatty liver disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known to scavenge reactive oxygen species (ROS) and decrease pro-inflammatory cytokine production, by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation...
November 1, 2017: Antioxidants (Basel, Switzerland)
Karumutchu Sitalu, B Hari Babu, J Naveena Lavanya Latha, A Lakshmana Rao
BACKGROUND: Caffeine, 1, 3, 7-trimethylxanthine is one of the xanthine derivatives that are for the most part utilized as a part of solutions as diuretics. The Cu (II) complexes have been synthesized from the N-heterocyclic carbene ligands. MATERIALS AND METHODS: The Cu (II) NHC complexes were characterized using analytical and spectral techniques. Antibacterial and antifungal activities of the Cu (II) NHC complexes were determined using the reported techniques...
2017: Pakistan Journal of Biological Sciences: PJBS
Bin Xiao, Xiao Deng, Grace G Y Lim, Shaoping Xie, Zhi Dong Zhou, Kah-Leong Lim, Eng-King Tan
Reactive oxygen species (ROS) and mitophagy are profoundly implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). Several studies have suggested that ROS are not involved in mitochondrial translocation of Parkin which primes mitochondria for autophagic elimination. However, whether ROS play a role in the execution of mitophagy is unknown. In the present study, we show that carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment induced both mitochondrial depolarization and generation of ROS that were needed for the mitophagy process...
October 12, 2017: Cell Death & Disease
Ovender Singh, Nidhi Tyagi, Marilyn M Olmstead, Kaushik Ghosh
Bio-inspired manganese [Mn(N5Py)(H2O)(CH3OH)](ClO4)2 (1) and iron [Fe(N5Py)(H2O)(ClO4)]ClO4 (2) complexes derived from a pentadentate ligand (N5Py = 2,6-bis((E)-1-phenyl-2-(pyridin-2-ylmethylene)hydrazinyl)pyridine) framework containing a N5 binding motif were synthesized and characterized using different spectroscopic methods. The molecular structures of complexes 1 and 2 were determined by X-ray crystallography. These complexes were found to be stable under physiological conditions and exhibited an excellent superoxide dismutase (SOD) activity...
October 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
Tomoya Shintani, Hirofumi Sakoguchi, Akihide Yoshihara, Ken Izumori, Masashi Sato
Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions...
December 2, 2017: Biochemical and Biophysical Research Communications
Saurav Bhowmick, Kelly L Drew
Cerebral ischemia-reperfusion (I/R) injury initiates a cascade of events, generating nitric oxide (NO) and superoxide(O2 •- ) to form peroxynitrite (ONOO- ), a potent oxidant. Arctic ground squirrels (AGS; Urocitellus parryii) show high tolerance to I/R injury. However, the underlying mechanism remains elusive. We hypothesize that tolerance to I/R modeled in an acute hippocampal slice preparation in AGS is modulated by reduced oxidative and nitrative stress. Hippocampal slices (400µm) from rat and AGS were subjected to oxygen glucose deprivation (OGD) using a novel microperfusion technique...
December 2017: Free Radical Biology & Medicine
Swetha Barkam, Julian Ortiz, Shashank Saraf, Nicholas Eliason, Rameech Mccormack, Soumen Das, Ankur Gupta, Craig Neal, Alex Petrovici, Cameron Hanson, Michael D Sevilla, Amitava Adhikary, Sudipta Seal
In this work, we tested our hypothesis that surface chemistry and antioxidant properties of cerium nanoparticles (CNPs) are affected by presence of counterions. We first employed various precursor cerium (III) (Ce(III)) salts with different counterions (acetate, nitrate, chloride, sulfate) to synthesize CNPs following the same wet chemical methodology. Electron spin resonance (ESR) studies provided evidence for the formation of radicals from counterions (e.g., NO3•(2-) from reduction of NO3(-) in CNPs synthesized from Ce(III) nitrate)...
September 14, 2017: Journal of Physical Chemistry. C, Nanomaterials and Interfaces
Rohit Gaurav, Jason T Varasteh, Michael R Weaver, Sean R Jacobson, Laura Hernandez-Lagunas, Qing Liu, Eva Nozik-Grayck, Hong Wei Chu, Rafeul Alam, Børge G Nordestgaard, Camilla J Kobylecki, Shoaib Afzal, Geoffrey L Chupp, Russell P Bowler
Oxidative stress is important in the pathogenesis of allergic asthma. Extracellular superoxide dismutase (EC-SOD; SOD3) is the major antioxidant in lungs, but its role in allergic asthma is unknown. Here we report that asthmatics have increased SOD3 transcript levels in sputum and that a single nucleotide polymorphism (SNP) in SOD3 (R213G; rs1799895) changes lung distribution of EC-SOD, and decreases likelihood of asthma-related symptoms. Knockin mice analogous to the human R213G SNP had lower airway hyperresponsiveness, inflammation, and mucus hypersecretion with decreased interleukin-33 (IL-33) in bronchoalveolar lavage fluid and reduced type II innate lymphoid cells (ILC2s) in lungs...
September 7, 2017: JCI Insight
Hongyan Dai, Meifang Wang, Parag N Patel, Theodore Kalogeris, Yajun Liu, William Durante, Ronald J Korthuis
Activation of large-conductance Ca2+ -activated K+ (BKCa ) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 h later. The goal of the present study was to determine the roles of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild-type (WT) or HO-1-null (HO-1-/- ) mice that were pretreated with NS-1619 or saline vehicle 24 h earlier...
November 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Kranti A Mapuskar, Kyle H Flippo, Joshua D Schoenfeld, Dennis P Riley, Stefan Strack, Taher Abu Hejleh, Muhammad Furqan, Varun Monga, Frederick E Domann, John M Buatti, Prabhat C Goswami, Douglas R Spitz, Bryan G Allen
Elderly cancer patients treated with ionizing radiation (IR) or chemotherapy experience more frequent and greater normal tissue toxicity relative to younger patients. The current study demonstrates that exponentially growing fibroblasts from elderly (old) male donor subjects (70, 72, and 78 years) are significantly more sensitive to clonogenic killing mediated by platinum-based chemotherapy and IR (∼70%-80% killing) relative to young fibroblasts (5 months and 1 year; ∼10%-20% killing) and adult fibroblasts (20 years old; ∼10%-30% killing)...
September 15, 2017: Cancer Research
Soledad Pitra, Javier E Stern
Recent studies have supported an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic, sympathetic, and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We have recently shown that PRR is expressed in VP neurons and that their activation increases neuronal activity...
September 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
Abeer M Mahmoud, Mohamed M Ali, Edwin R Miranda, Jacob T Mey, Brian K Blackburn, Jacob M Haus, Shane A Phillips
Insulin resistance promotes vascular endothelial dysfunction and subsequent development of cardiovascular disease. Previously we found that skeletal muscle arteriolar flow-induced dilation (FID) was reduced following a hyperinsulinemic clamp in healthy adults. Therefore, we hypothesized that hyperinsulinemia, a hallmark of insulin resistance, contributes to microvascular endothelial cell dysfunction via inducing oxidative stress that is mediated by NADPH oxidase (Nox) system. We examined the effect of insulin, at levels that are comparable with human hyperinsulinemia on 1) FID of isolated arterioles from human skeletal muscle tissue in the presence and absence of Nox inhibitors and 2) human adipose microvascular endothelial cell (HAMECs) expression of nitric oxide (NO), endothelial NO synthase (eNOS), and Nox-mediated oxidative stress...
June 3, 2017: Redox Biology
Thássio R R Mesquita, Gianne P Campos-Mota, Virgínia S Lemos, Jader S Cruz, Itamar C G de Jesus, Enilton A Camargo, Jorge L Pesquero, João B Pesquero, Luciano Dos Santos A Capettini, Sandra Lauton-Santos
B1- and B2-kinin receptors are G protein-coupled receptors that play an important role in the vascular function. Therefore, the present study was designed to evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced vascular relaxation, focusing on the protein-protein interaction involving kinin receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS). Vascular reactivity, nitric oxide (NO·) and reactive oxygen species (ROS) generation, co-immunoprecipitation were assessed in thoracic aorta from male wild-type (WT), B1- (B1R(-/-)), B2- (B2R(-/-)) knockout mice...
2017: Frontiers in Physiology
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