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Nitric Oxide: Biology and Chemistry

Gregory R Buchan, Gustavo Bonacci, Marco Fazzari, Sonia Salvatore, Stacy Gelhaus Wendell
Nitro-fatty acids (NO2 -FA) are pleiotropic modulators of redox signaling pathways. Their effects on inflammatory signaling have been studied in great detail in cell, animal and clinical models primarily using exogenously administered nitro-oleic acid. While we know a great deal about their signaling, endogenous NO2 -FA formation and metabolism is relatively unexplored. This review will cover what is currently known regarding proposed mechanisms of formation, dietary modulation of endogenous NO2 -FA levels, and pathways of metabolism and detection of NO2 FA and corresponding metabolites...
July 10, 2018: Nitric Oxide: Biology and Chemistry
Kenji Obayashi, Norio Kurumatani, Keigo Saeki
The association between chronic kidney disease (CKD), serum levels of asymmetric dimethylarginine (ADMA), and sleep quality has not been studied in large populations. In this cross-sectional study of 1115 elderly individuals (mean age, 71.9 years), we measured serum levels of ADMA, and objective and subjective sleep quality using actigraphy and a standardized self-reported questionnaire, respectively. Multivariable analysis adjusted for potential confounders revealed that in females, compared with the non-CKD/low-ADMA group (n=312), sleep efficiency was significantly lower in the CKD/high-ADMA group (n=52) by 3...
July 3, 2018: Nitric Oxide: Biology and Chemistry
Hiviny de Ataides Raquel, Nathalia Zerbinatti Ferreira, Bruno Fernando Cruz Lucchetti, Bárbara Falquetto, Phileno Pinge-Filho, Lisete Compagno Michelini, Marli Cardoso Martins-Pinge
Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p...
July 3, 2018: Nitric Oxide: Biology and Chemistry
Francisco J Schopfer, Dario A Vitturi, Diane K Jorkasky, Bruce A Freeman
Nitrated oleic acid (NO2 -OA) was first identified in 2003, and after the characterization of its formation and thiol reactivity, it was used as a prototypical molecule to investigate the physiological actions of endogenous nitrated fatty acids (NO2 -FA). Based on in vitro observations showing significant activation of cytoprotective and anti-inflammatory signaling responses by NO2 -FA, experiments were designed to determine their pharmacological potential. Supported by strong intellectual protection and favorable pharmacokinetic and pharmacodynamic data, 10-NO2 -OA (CXA-10) underwent pharmaceutical development as a drug to treat fibrotic and inflammatory diseases...
June 23, 2018: Nitric Oxide: Biology and Chemistry
Chun-Wen Su, Ming-Hsien Chien, Chiao-Wen Lin, Mu-Kuan Chen, Jyh-Ming Chow, Chun-Yi Chuang, Chia-Hsuan Chou, Yu-Cheng Liu, Shun-Fa Yang
Oral cancer is a major head and neck cancer that is reported to be causally associated with genetic factors and environmental carcinogens. Endothelial nitric oxide synthase (eNOS) was reported to modulate carcinogenesis and progression through nitric oxide (NO) production. Genetic polymorphisms in the eNOS gene can regulate its transcription and further mediate NO production. The purpose of this study was to explore the influences of eNOS gene polymorphisms combined with environmental carcinogens on the predisposition for oral cancer...
June 19, 2018: Nitric Oxide: Biology and Chemistry
Xiaohong Liu, Xin Xu, Ruru Shang, Yingjie Chen
Patients with chronic kidney disease have an increased cardiovascular morbidity and mortality. It has been recognized that the traditional cardiovascular risk factors could only partially explain the increased cardiovascular morbidity and mortality in patients with chronic kidney disease. Asymmetric dimethylarginine (ADMA) and N-monomethy l-arginine (L-NMMA) are endogenous inhibitors of nitric oxide synthases that attenuate nitric oxide production and enhance reactive oxidative specie generation. Increased plasma ADMA and/or L-NMMA are strong and independent risk factor for chronic kidney disease, and various cardiovascular diseases such as hypertension, coronary artery disease, atherosclerosis, diabetes, and heart failure...
June 19, 2018: Nitric Oxide: Biology and Chemistry
Pooja, Dishari Ghosh, Kalpana Bhargava, Niroj Kumar Sethy
The lower inhaled oxygen per volume at high altitude poses an intimidating challenge for humans to survive and reproduce. Indigenous populations of the Himalayas reportedly exhibit higher microcirculatory blood flow accompanied by higher orders of magnitude of nitric oxide (NO) products in lung, plasma and red blood cells as a vascular adaptation strategy for hypobaric hypoxia. The precise mechanism of such observed higher NO metabolites for hypoxia adaptation remains elusive. Studying high altitude native Ladakhi women, we observed significant higher eNOS mRNA and protein in blood/plasma as compared to lowland women...
June 9, 2018: Nitric Oxide: Biology and Chemistry
Abeer Shaalan, Guy Carpenter, Gordon Proctor
AIM: Inducible nitric oxide synthase (iNOS) is a key regulator of the innate immune system. The aim of the current study was to explore whether innate immune-mediated iNOS and reactive nitrogen species acutely perturb acinar cell physiology and calcium homeostasis of exocrine salivary tissues. METHODS: Innate immunity in the submandibular gland of C57BL/6 mice was locally activated via intraductal retrograde infusion of polyinosinic:polycytidylic acid (poly (I:C)...
June 7, 2018: Nitric Oxide: Biology and Chemistry
Michael Koennecke, Frederick Benecke, Anja Masche, Robert Linke, Karl-Ludwig Bruchhage, Ralph Pries, Ludger Klimek, Barbara Wollenberg
INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a significant health problem, but the pathogenesis remains unclear to date. Nitric oxide (NO) has known airway modulating functions. Therefore, we investigated nitric oxide production to determine the role of eNOS in nasal polyps, with additional analysis of the effect of the monoterpene oxide 1,8-cineol on the possible regulation of eNOS signaling and thus NO production. METHODS: We determined eNOS expression, as well as regulatory and effector proteins like NOSTRIN and CASP8, using whole genome microarray, immunohistochemistry and western blot...
June 6, 2018: Nitric Oxide: Biology and Chemistry
Aaron C Schneider, William E Hughes, Kenichi Ueda, Joshua M Bock, Darren P Casey
The vasoactive molecule nitric oxide (NO) contributes to regulation of blood pressure (BP) at rest and during exercise. Age-related exaggerated increased BP responses during exercise have been proposed to be due in part to a decreased NO bioavailability and possibly an enhanced skeletal muscle metaboreflex. In the present study we sought to determine if age-related differences in BP responses to skeletal muscle metaboreflex activation exist. Additionally, since NO bioavailability can be improved with exogenous nitrate (NO3 - ) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO3 - supplementation would reduce BP responses to muscle metaboreflex activation in healthy older adults...
June 1, 2018: Nitric Oxide: Biology and Chemistry
E S Buys, D P Zimmer, J Chickering, R Graul, Y T Chien, A Profy, J R Hadcock, J L Masferrer, G T Milne
Nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC), an enzyme that catalyzes the conversion of guanosine-5'-triphosphate (GTP) to cyclic guanosine-3',5'-monophophate (cGMP), transduces many of the physiological effects of the gasotransmitter NO. Upon binding of NO to the prosthetic heme group of sGC, a conformational change occurs, resulting in enzymatic activation and increased production of cGMP. cGMP modulates several downstream cellular and physiological responses, including but not limited to vasodilation...
May 31, 2018: Nitric Oxide: Biology and Chemistry
Simone de Araújo, Ana P Oliveira, Francisca B M Sousa, Luan K M Souza, Gabriella Pacheco, Marcelo C Filgueiras, Lucas A D Nicolau, Gerly Anne C Brito, Gilberto S Cerqueira, Renan O Silva, Marcellus H L P Souza, Jand Venes R Medeiros
Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2 S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol...
May 30, 2018: Nitric Oxide: Biology and Chemistry
Ayuka Ehara, Kazuhiko Nakadate, Hiroyuki Sugimoto, Kanji Yoshimoto, Shuichi Ueda
Neuronal nitric oxide synthase (nNOS) is involved in nigrostriatal dopaminergic (DA) neurodegeneration. However, little is known about the distribution patterns and functions of nNOS in slowly progressive DA neurodegeneration. Here we describe the spatiotemporal change in nNOS expression over the course of neurodegeneration and the effect of short- or long-term treatment with the nNOS inhibitor, 7-nitroindazole (7-NI), in zitter (zi/zi) rats. In the substantia nigra pars compacta (SNc), nNOS expression was significantly increased with progression of neurodegeneration...
May 22, 2018: Nitric Oxide: Biology and Chemistry
Sho Kobayashi, Shinji Hamashima, Takujiro Homma, Mami Sato, Ryosuke Kusumi, Shiro Bannai, Junichi Fujii, Hideyo Sato
The amino acid transport system xc - is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system xc - , xCT, is strongly induced by various stimuli, including oxidative stress and bacterial lipopolysaccharides (LPS) in macrophages. In the present study, we investigated the production of nitric oxide by LPS-stimulated mouse peritoneal macrophages isolated from both xCT-deficient and wild-type mice. After culturing macrophages in the presence of LPS for 24-48 h, nitrite levels in the medium of xCT-deficient macrophages were significantly decreased compared to that of wild-type cells...
May 21, 2018: Nitric Oxide: Biology and Chemistry
Colin Borland, Geoff Moggridge, Ruhi Patel, Suhani Patel, Qingyu Zhu, Alain Vuylsteke
A simple diffusion cell was made to measure the permeability and diffusivity of Nitric Oxide in human plasma and red cells. Nitric oxide was passed through the cell containing plasma or nitrited red cells enclosed by silicone membranes. Steady state permeability (αNO DNO ) was calculated from the cell dimensions and from the NO bulk flow entering and leaving the cell. The diffusion coefficient (DNO ) was calculated in three ways: (i) by dividing the steady state permeability by published values for solubility (αNO ) in water at 26 °C and 37 °C (ii) by a numerical method and (iii) by an analytical method...
May 19, 2018: Nitric Oxide: Biology and Chemistry
Guilherme B Nogueira, Giovana R Punaro, Clemerson S Oliveira, Fabiane R Maciel, Thamires O Fernandes, Deyse Y Lima, Adelson M Rodrigues, Margaret G Mouro, Sergio R R Araujo, Elisa M S Higa
The diabetes mellitus (DM) induces several changes, with substantial increase of reactive oxygen species (ROS). The ROS cause damage to systemic and renal microvasculature, which could be one of the mechanisms involved in the development of diabetic nephropathy (DN). The ROS modulate other substances like the nitric oxide (NO), a vasodilator with important role in the renal function. N-acetylcysteine (NAC) is an antioxidant that acts replenishing intracellular cysteine levels, which is essential for glutathione formation...
May 18, 2018: Nitric Oxide: Biology and Chemistry
Yaqi Shen, Zhuqing Shen, Lingyan Guo, Qiuyan Zhang, Zhijun Wang, Lei Miao, Minjun Wang, Jian Wu, Wei Guo, Yizhun Zhu
AIMS: Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (H2 S) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of H2 S in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and H2 S generation...
May 17, 2018: Nitric Oxide: Biology and Chemistry
Anne Sömmer, Sönke Behrends
Soluble guanylyl cyclase (sGC) is a heterodimeric enzyme consisting of one α and one β subunit. The α1 β1 (GC-1) and α2 β1 (GC-2) heterodimers are important for NO signaling in humans and catalyse the conversion from GTP to cGMP. Each sGC subunit consists of four domains. Several crystal structures of the isolated domains are available. However, crystals of full-length sGC have failed to materialise. In consequence, the detailed three dimensional structure of sGC remains unknown to date. Different techniques including stopped-flow spectroscopy, Förster-resonance energy transfer, direct fluorescence, analytical ultracentrifugation, chemical cross-linking, small-angle X-ray scattering, electron microscopy, hydrogen-deuterium exchange and protein thermal shift assays, were used to collect indirect information...
April 26, 2018: Nitric Oxide: Biology and Chemistry
Bruce A Freeman, Valerie B O'Donnell, Francisco J Schopfer
Foundational advances in eicosanoid signaling, the free radical biology of oxygen and nitric oxide and mass spectrometry all converged to enable the discovery of nitrated unsaturated fatty acids. Due to the unique biochemical characteristics of fatty acid nitroalkenes, these species undergo rapid and reversible Michael addition of biological nucleophiles such as cysteine, leading to the post-translational modification of low molecular weight and protein thiols. This capability has led to the present understanding that nitro-fatty acid reaction with the alkylation-sensitive cysteine proteome leads to physiologically-beneficial alterations in transcriptional regulatory protein function, gene expression and in vivo rodent model responses to metabolic and inflammatory stress...
July 1, 2018: Nitric Oxide: Biology and Chemistry
Peter Sandner, Eva-Maria Becker-Pelster, Johannes Peter Stasch
The NO/sGC/cGMP signaling cascade plays a pivotal role in regulation of cardiovascular, cardiopulmonary and cardiorenal diseases and impairment of this cascade results in severe pathologies. Therefore, pharmacological interventions, targeting this pathway are promising strategies for treating a variety of diseases. Nitrates, supplementing NO and, PDE5 inhibitors preventing cGMP degradation, are used for angina pectoris treatment and the treatment of pulmonary arterial hypertension (PAH), respectively. More recently, a new class of drugs which directly stimulate the sGC enzyme and trigger NO-independent cGMP production was introduced and termed sGC stimulators...
July 1, 2018: Nitric Oxide: Biology and Chemistry
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