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Peroxynitrite, lung disease

Harshavardhan Kenche, Zhi-Wei Ye, Kokilavani Vedagiri, Dylan M Richards, Xing-Huang Gao, Kenneth D Tew, Danyelle M Townsend, Anna Blumental-Perry
Identification of factors contributing to the development of chronic obstructive pulmonary disease (COPD) is crucial for developing new treatments. An increase in the levels of protein-disulfide isomerase (PDI), a multifaceted endoplasmic reticulum resident chaperone, has been demonstrated in human smokers, presumably as a protective adaptation to cigarette smoke (CS) exposure. We found a similar increase in the levels of PDI in the murine model of COPD. We also found abnormally high levels (4-6 times) of oxidized and sulfenilated forms of PDI in the lungs of murine smokers compared with non-smokers...
February 26, 2016: Journal of Biological Chemistry
Norbert Weissmann, Borja Lobo, Alexandra Pichl, Nirmal Parajuli, Michael Seimetz, Raquel Puig-Pey, Elisabet Ferrer, Víctor I Peinado, David Domínguez-Fandos, Athanasios Fysikopoulos, Johannes-Peter Stasch, Hossein A Ghofrani, Núria Coll-Bonfill, Reiner Frey, Ralph T Schermuly, Jéssica García-Lucio, Isabel Blanco, Mariola Bednorz, Olga Tura-Ceide, Elsa Tadele, Ralf P Brandes, Jan Grimminger, Walter Klepetko, Peter Jaksch, Robert Rodriguez-Roisin, Werner Seeger, Friedrich Grimminger, Joan A Barberà
RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available. OBJECTIVES: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions. METHODS: Investigations were performed in human lung tissue from patients with COPD, healthy donors, mice, and guinea pigs...
June 1, 2014: American Journal of Respiratory and Critical Care Medicine
Carla M Prado, Mílton A Martins, Iolanda F L C Tibério
Asthma is a chronic inflammatory airway disease characterized by allergen-induced airway hyperresponsiveness, airway inflammation, and remodeling. Nitric oxide (NO) derived from constitutive and inducible enzymes affects many aspects of asthma physiopathology. Animal in vivo studies have indicated that inhibition of iNOS may play a central role in the modulation of these features, particularly extracellular matrix remodeling. Additionally, increases in iNOS-derived NO, observed in asthmatic patients, may lead to an increase in peroxynitrite and an imbalance of oxidant and antioxidant pathways...
2011: ISRN Allergy
Umit M Sahiner, Esra Birben, Serpil Erzurum, Cansin Sackesen, Omer Kalayci
Asthma is a chronic inflammatory lung disease that results in airflow limitation, hyperreactivity, and airway remodeling. There is strong evidence that an imbalance between the reducing and oxidizing systems favoring a more oxidative state is present in asthma. Endogenous and exogenous reactive oxygen species, such as superoxide anion, hydroxyl radical, hypohalite radical, and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide, peroxynitrite, and nitrite, play a major role in the airway inflammation and are determinants of asthma severity...
October 2011: World Allergy Organization Journal
Hiroki Yokoo, Seiichi Chiba, Kengo Tomita, Michinori Takashina, Hiroshi Sagara, Saburo Yagisita, Yasuo Takano, Yuichi Hattori
Sepsis is a major clinical challenge and septic encephalopathy is its nasty complication. The pathogenesis and underlying mechanisms of septic encephalopathy are not well understood. This study sought to fully characterize sepsis-associated biochemical and histopathological changes in brains of mice after cecal ligation and puncture, regarded as a highly clinically relevant animal model of polymicrobial sepsis. Real-time PCR analysis showed that gene expression levels of proinflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were significantly up-regulated in brain tissues from septic mice, but to a much lesser extent when compared with those in peripheral tissues such as lungs...
2012: PloS One
Masahiro Enomoto, Kiran Gosal, Elena Cubells, Javier Escobar, Maximo Vento, Robert P Jankov, Jaques Belik
BACKGROUND: Chronic exposure to supplemental oxygen (O(2)) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature. METHODS: Following 1-h 100% O(2) exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated...
November 2012: Pediatric Research
Feng Ru Tang, Weng Keong Loke
Victims exposed to sulfur mustard (HD) in World War I and Iran-Iraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in Iran-Iraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases...
September 2012: Critical Reviews in Toxicology
Hisatoshi Sugiura, Hiroki Kawabata, Tomohiro Ichikawa, Akira Koarai, Satoru Yanagisawa, Takashi Kikuchi, Yoshiaki Minakata, Kazuto Matsunaga, Masanori Nakanishi, Tsunahiko Hirano, Keiichiro Akamatsu, Kanako Furukawa, Masakazu Ichinose
The anti-inflammatory effects of theophylline have been reported to include inhibition of the release of proinflammatory mediators from macrophages and neutrophils. Overproduction of reactive nitrogen species (RNS) has been reported in the airways of patients with chronic obstructive pulmonary disease (COPD), and this causes tissue inflammation and injury. We investigated whether peroxynitrite stimulated the release of matrix metalloproteinases 2 and 9 (MMP-2 and -9; gelatinases) from human fetal lung fibroblasts (HFL-1 cell line) and whether theophylline inhibited the peroxynitrite-augmented release of MMPs...
April 15, 2012: American Journal of Physiology. Lung Cellular and Molecular Physiology
Nicole J Gentner, Lynn P Weber
Chronic smoking and secondhand tobacco smoke exposure are major risk factors for cardiovascular disease that are known to adversely alter the structural and mechanical properties of arteries. The objective of this study was to determine the effects of subchronic secondhand tobacco smoke exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in conscious, unsedated radiotelemetry-implanted rats. Pulse wave change in pressure over time (dP/dt) was used an indicator of arterial stiffness and was compared with both structural (wall thickness) and functional (nitric oxide production and bioactivity and endothelin-1 levels) features of the arterial wall...
February 1, 2012: American Journal of Physiology. Heart and Circulatory Physiology
Danli Wu, Patricia Yotnda
Reactive oxygen species include a number of molecules that damage DNA and RNA and oxidize proteins and lipids (lipid peroxydation). These reactive molecules contain an oxygen and include H(2;)O(2;) (hydrogen peroxide), NO (nitric oxide), O(2;)(-) (oxide anion), peroxynitrite (ONOO(-)), hydrochlorous acid (HOCl), and hydroxyl radical (OH(-)). Oxidative species are produced not only under pathological situations (cancers, ischemic/reperfusion, neurologic and cardiovascular pathologies, infectious diseases, inflammatory diseases, autoimmune diseases , etc…) but also during physiological (non-pathological) situations such as cellular metabolism...
2011: Journal of Visualized Experiments: JoVE
Charles A Downs, David W Montgomery, Carrie J Merkle
Cigarette smoke causes oxidative stress in the lung resulting in injury and disease. The purpose of this study was to determine if there were age-related differences in cigarette smoke extract (CSE)-induced production of reactive species in single and co-cultures of alveolar epithelial type I (AT I) cells and microvascular endothelial cells harvested from the lungs (MVECLs) of neonatal, young and old male Fischer 344 rats. Cultures of AT I cells and MVECLs grown separately (single culture) and together (co-culture) were exposed to CSE (1, 10, 50, 100%)...
November 2011: Microvascular Research
Michael Seimetz, Nirmal Parajuli, Alexandra Pichl, Florian Veit, Grazyna Kwapiszewska, Friederike C Weisel, Katrin Milger, Bakytbek Egemnazarov, Agnieszka Turowska, Beate Fuchs, Sandeep Nikam, Markus Roth, Akylbek Sydykov, Thomas Medebach, Walter Klepetko, Peter Jaksch, Rio Dumitrascu, Holger Garn, Robert Voswinckel, Sawa Kostin, Werner Seeger, Ralph T Schermuly, Friedrich Grimminger, Hossein A Ghofrani, Norbert Weissmann
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. We report in an emphysema model of mice chronically exposed to tobacco smoke that pulmonary vascular dysfunction, vascular remodeling, and pulmonary hypertension (PH) precede development of alveolar destruction. We provide evidence for a causative role of inducible nitric oxide synthase (iNOS) and peroxynitrite in this context. Mice lacking iNOS were protected against emphysema and PH. Treatment of wild-type mice with the iNOS inhibitor N(6)-(1-iminoethyl)-L-lysine (L-NIL) prevented structural and functional alterations of both the lung vasculature and alveoli and also reversed established disease...
October 14, 2011: Cell
Tamás Radovits, Carsten J Beller, John T Groves, Béla Merkely, Matthias Karck, Csaba Szabó, Gábor Szabó
OBJECTIVE: Peroxynitrite, a toxic nitrogen species, has been implicated in the development of ischemia/reperfusion injury. The aim of the present study was to investigate the effects of the potent peroxynitrite decomposition catalyst, FP15, on myocardial, endothelial, and pulmonary function in an experimental model of cardioplegic arrest and extracorporal circulation. METHODS: Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started and either saline vehicle (control, n = 6) or FP15 (n = 6) was administered...
February 2012: European Journal of Cardio-thoracic Surgery
Sébastien Hulo, Hélène Tiesset, Steve Lancel, Jean Louis Edmé, Benoit Viollet, Annie Sobaszek, Rémi Nevière
BACKGROUND: Acute ozone exposure causes lung oxidative stress and inflammation leading to lung injury. At least one mechanism underlying the lung toxicity of ozone involves excessive production of reactive oxygen and nitrogen intermediates such as peroxynitrite. In addition and beyond its major prooxidant properties, peroxynitrite may nitrate tyrosine residues altering phosphorylation of many protein kinases involved in cell signalling. It was recently proposed that peroxynitrite activates 5'-AMP-activated kinase (AMPK), which regulates metabolic pathways and the response to cell stress...
2011: Respiratory Research
Hisatoshi Sugiura, Masakazu Ichinose
Since the discovery of nitric oxide (NO), an intracellular signal transmitter, the role of NO has been investigated in various organs. In the respiratory system, NO derived from the constitutive type of NO synthase (cNOS, NOS1, NOS3) induces bronchodilation and pulmonary vasodilatation to maintain homeostasis. In contrast, the roles of excessive NO derived from the inducible type of NOS (iNOS, NOS2) in airway and lung inflammation in inflammatory lung diseases including bronchial asthma and chronic obstructive pulmonary disease (COPD) are controversial...
August 1, 2011: Nitric Oxide: Biology and Chemistry
Saurabh Aggarwal, Christine M Gross, Sanjiv Kumar, Sanjeev Datar, Peter Oishi, Gokhan Kalkan, Christian Schreiber, Sohrab Fratz, Jeffrey R Fineman, Stephen M Black
Pulmonary vasodilation is mediated through the activation of protein kinase G (PKG) via a signaling pathway involving nitric oxide (NO), natriuretic peptides (NP), and cyclic guanosine monophosphate (cGMP). In pulmonary hypertension secondary to congenital heart disease, this pathway is endogenously activated by an early vascular upregulation of NO and increased myocardial B-type NP expression and release. In the treatment of pulmonary hypertension, this pathway is exogenously activated using inhaled NO or other pharmacological agents...
December 2011: Journal of Cellular Physiology
Ejaife O Agbani, Paul Coats, Roger M Wadsworth
There is separate evidence for peroxynitrite formation and hypoxia-induced cell proliferation in several models of hypoxic pulmonary hypertension. We therefore hypothesized that the stimulation of pulmonary artery smooth muscle cells (PASMCs) proliferation by hypoxia is due to peroxynitrite formation. The effect of hypoxia alone and in combination with ≤ 0.2 μM peroxynitrite on PASMCs was investigated in explants from bovine lungs grown in 1%, 5%, or 10% oxygen for 24 hours with or without peroxynitrite...
May 2011: Journal of Cardiovascular Pharmacology
Francisco Garcia Soriano, Clara Batista Lorigados, Pal Pacher, Csaba Szabó
Excessive free-radical production due to various bacterial components released during bacterial infection has been linked to cell death and tissue injury. Peroxynitrite is a highly reactive oxidant produced by the combination of nitric oxide (NO) and superoxide anion, which has been implicated in cell death and tissue injury in various forms of critical illness. Pharmacological decomposition of peroxynitrite may represent a potential therapeutic approach in diseases associated with the overproduction of NO and superoxide...
June 2011: Shock
Aditya Venugopal, Ruslana Bryk, Shuangping Shi, Kyu Rhee, Poonam Rath, Dirk Schnappinger, Sabine Ehrt, Carl Nathan
Mycobacterium tuberculosis (Mtb) adapts to persist in a nutritionally limited macrophage compartment. Lipoamide dehydrogenase (Lpd), the third enzyme (E3) in Mtb's pyruvate dehydrogenase complex (PDH), also serves as E1 of peroxynitrite reductase/peroxidase (PNR/P), which helps Mtb resist host-reactive nitrogen intermediates. In contrast to Mtb lacking dihydrolipoamide acyltransferase (DlaT), the E2 of PDH and PNR/P, Lpd-deficient Mtb is severely attenuated in wild-type and immunodeficient mice. This suggests that Lpd has a function that DlaT does not share...
January 20, 2011: Cell Host & Microbe
Matthias Lange, Csaba Szabo, Perenlei Enkhbaatar, Rhykka Connelly, Eszter Horvath, Atsumori Hamahata, Robert A Cox, Aimalohi Esechie, Yoshimitsu Nakano, Lillian D Traber, David N Herndon, Daniel L Traber
During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting with superoxide radicals, yielding the reactive nitrogen species peroxynitrite (ONOO(-)). ONOO(-) exerts cytotoxic effects, among others, by nitrating/nitrosating proteins and lipids, by activating the nuclear repair enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect of the ONOO(-) decomposition catalyst INO-4885 on the development of lung injury in chronically instrumented sheep with combined burn and smoke inhalation injury...
February 2011: American Journal of Physiology. Lung Cellular and Molecular Physiology
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