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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 17, 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 16, 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...
May 6, 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...
May 5, 2018: Nitric Oxide: Biology and Chemistry
Lauren K Wareham, Emmanuel S Buys, Rebecca M Sappington
Glaucoma is a prevalent optic neuropathy characterized by the progressive dysfunction and loss of retinal ganglion cells (RGCs) and their optic nerve axons leading to irreversible visual field loss. Multiple risk factors for the disease have been identified, but elevated intraocular pressure (IOP) remains the primary risk factor amenable to treatment. Reducing IOP however does not always prevent glaucomatous neurodegeneration, and many patients progress with the disease despite having IOP in the normal range...
April 30, 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
Murugaeson R Kumar, Tara Clover, Abayomi D Olaitan, Christopher Becker, Touradj Solouki, Patrick J Farmer
Several recent reports suggest that HNO may be produced endogenously by reaction of H2 S and S-nitrosoglutathione (GSNO). This hypothesis was tested using deoxymyoglobin (MbFeII ) to trap the expected HNO released from the target reaction, which should generate the stable HNO adduct, HNO-Mb, under anaerobic conditions. Under numerous experimental conditions, the sole globin product was NO-Mb, as characterized by absorbance, EPR, and NMR spectroscopies. Analogous reactions of GSNO with other biological reductants such as ascorbic acid, dithiothreitol, glutathione, and dithionite also yielded NO-Mb as the sole globin product; however, whereas analogous reduction of GSNO using NaBH4 generates HNO-Mb in high yield...
April 25, 2018: Nitric Oxide: Biology and Chemistry
Benjamin G Horst, Michael A Marletta
Soluble guanylate cyclase (sGC) is responsible for transducing the gaseous signaling molecule nitric oxide (NO) into the ubiquitous secondary signaling messenger cyclic guanosine monophosphate in eukaryotic organisms. sGC is exquisitely tuned to respond to low levels of NO, allowing cells to respond to non-toxic levels of NO. In this review, the structure of sGC is discussed in the context of sGC activation and deactivation. The sequence of events in the activation pathway are described into a comprehensive model of in vivo sGC activation as elucidated both from studies with purified enzyme and those done in cells...
April 25, 2018: Nitric Oxide: Biology and Chemistry
Balasubramanian Palaniappan, Uma Sundaram
Pharmacological manipulations of constitutive nitric oxide (cNO) levels have been shown to have variable effects on Na absorption in vivo and in vitro in different tissues. Species differences, untoward in vivo effects (e.g. ENS, blood flow) and pharmacological non-specificity may account for these confounding observations. Thus, to directly and specifically determine the effect of cNO on brush border membrane Na/H exchange (NHE3) and Na-dependent glucose co-transport (SGLT-1), we inhibited cNO synthase (cNOS) with its siRNA in rat small intestinal epithelial cells (IEC-18) in vitro...
April 24, 2018: Nitric Oxide: Biology and Chemistry
Kenneth C Childers, Elsa D Garcin
Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in smooth muscle cells and maintains vascular function by inducing vasorelaxation in nearby blood vessels. GC-1 converts guanosine 5'-triphosphate (GTP) into cyclic guanosine 3',5'-monophosphate (cGMP), which acts as a second messenger to improve blood flow. While much work has been done to characterize this pathway, we lack a mechanistic understanding of how NO binding to the heme domain leads to a large increase in activity at the C-terminal catalytic domain...
April 24, 2018: Nitric Oxide: Biology and Chemistry
Rixing Zhan, Fan Wang, Ying Wu, Ying Wang, Wei Qian, Menglong Liu, Tengfei Liu, Weifeng He, Hui Ren, Gaoxing Luo
OBJECTIVE: Nitric oxide (NO) has emerged as a critical molecule in wound healing, but the mechanism underlying its activity is not well defined. Here, we explored the effect of NO on the de-adhesion of epidermal stem cells (ESCs) and the mechanism involved in this process. METHODS: The effects of NO on isolated human and mouse ESCs cultured in the presence of different concentrations of the NO donor S-nitroso-N-acetyl penicillamine (SNAP) were evaluated in cell de-adhesion assays mediated by integrin β and collagen IV...
April 23, 2018: Nitric Oxide: Biology and Chemistry
Michael Russwurm, Doris Koesling
The intracellular messenger molecule cGMP has an established function in the regulation of numerous physiological events. Yet for the identification of further biological cGMP-mediated functions, precise information whether a cGMP response exists in a certain cell type or tissue is mandatory. In this review, the techniques to measure cGMP i.e. cGMP-formation, -degradation or -levels are outlined and discussed. As a superior method to measure cGMP, the article focusses on FRET-based cGMP indicators, describes the different cGMP-indicators and discusses their advantages and drawbacks...
April 20, 2018: Nitric Oxide: Biology and Chemistry
Jorge Miguel Romero, María Elena Carrizo, Juan Agustín Curtino
Triosephosphate isomerase (TPI), the glycolytic enzyme that catalyzes the isomerization of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P), has been frequently identified as a target of S-nitrosylation by proteomic studies. However, the effect of S-nitrosylation on its activity has only been explored in plants and algae. Here, we describe the in vitro S-nitrosylation of human TPI (hTPI), and the effect of the modification on its enzymatic parameters. NO-incorporation into the enzyme cysteine residues occurred by a time-dependent S-transnitrosylation from both, S-nitrosocysteine (CySNO) and S-nitrosoglutathione (GSNO), with CySNO being the more efficient NO-donor...
April 17, 2018: Nitric Oxide: Biology and Chemistry
Oliver Baum, Dea Aaldijk, Anna Lena Engeli, Matthias Spree, Serge Summermatter, Christoph Handschin, Andreas Zakrzewicz
The expression of neuronal NO synthase (nNOS) alpha- and beta-isoforms in skeletal muscle is well documented but only little information is available about their regulation/functions. Using different mouse models, we now assessed whether the expression of nNOS-isoforms in muscle fibers is related to mitochondria content/activity and regulated by peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Catalytic histochemistry revealed highest nNOS-concentrations to be present in type-2 oxidative muscle fibers...
April 17, 2018: Nitric Oxide: Biology and Chemistry
Zi-Chao Wang, Yuzhen Yan, Ping Su, Mou-Ming Zhao, Ning Xia, De-Wei Chen
BACKGROUND: To find a succedaneum of present methods for slaughtering tilapia, we have demonstrated the influence of nitric oxide (NO) (saturated NO solution) through euthanasia before slaughter on the animal welfare and muscle color of tilapia. The results suggested that NO euthanasia significantly improved the animal welfare and muscle color. Besides, the investigation of NO postmortem treatment on the muscle color and color stability of tilapia fillets suggested that NO postmortem treatment not only improved the muscle color and color stability but also prolonged the shelf-life of tilapia fillets during the refrigerated storage...
April 7, 2018: Nitric Oxide: Biology and Chemistry
Andreas Friebe, Barbara Voußen, Dieter Groneberg
Nitric oxide-sensitive guanylyl cyclase (NO-GC) has been shown to regulate a plethora of different functions in the body. These include, among many others, the fine-tuning of vascular tone, platelet reactivity and gastrointestinal motility. Evidence for the participation of NO-GC in these functions has been obtained from various species including humans, rodents, as well as insects. Clearly, individual cell types that express NO-GC contribute differentially to organ-specific NO/cGMP signaling in the body. Hence, identification of NO-GC-expressing cells and their individual involvement in NO/cGMP signaling constituted the focus of many studies over the last 40 years...
April 4, 2018: Nitric Oxide: Biology and Chemistry
Nikolaos Pitsikas
Anxiety-related disorders are a common public health issues. Current medication for this affective disorder involves the GABA-ergic or the serotonergic transmission. Different forms of anxiety, however, are resistant to treatment with GABA-ergic or serotonergic agents and the use of these compounds can be associated with severe side effects. Thus, almost 60 years after the discovery of the benzodiazepines there is need not only for fresh medications but also alternative targets. The nitrergic system has emerged as a promising target since several lines of evidence suggest that nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is implicated in anxiety...
April 3, 2018: Nitric Oxide: Biology and Chemistry
Soma Jobbagy, Roderick J Tan
The kidneys are vital organs responsible for maintaining body fluid homeostasis within proper physiologic ranges. Kidney disease is an epidemic clinical problem causing significant morbidity and mortality, and current treatments are limited to renin-angiotensin system blockade or renal replacement therapy for the majority of affected individuals. There is a critical, unmet need for novel pharmacological agents to improve the outcome of patients with kidney disease. Nitro-oleic acid (NO2 -OA) is an endogenously generated electrophilic compound with the capacity to modify thiols in proteins, altering their function...
March 29, 2018: Nitric Oxide: Biology and Chemistry
Capilla Mata-Pérez, María N Padilla, Beatriz Sánchez-Calvo, Juan C Begara-Morales, Raquel Valderrama, Mounira Chaki, Juan B Barroso
Nitro-fatty acids (NO2 -FAs) are formed from the reaction between nitrogen dioxide (NO2 ) and mono and polyunsaturated fatty acids. Knowledge concerning NO2 -FAs has significantly increased within a few years ago and the beneficial actions of these species uncovered in animal systems have led to consider them as molecules with therapeutic potential. Based on their nature and structure, NO2 -FAs have the ability to release nitric oxide (NO) in aqueous environments and the capacity to mediate post-translational modifications (PTM) by nitroalkylation...
March 27, 2018: Nitric Oxide: Biology and Chemistry
Jana Wobst, Heribert Schunkert, Thorsten Kessler
In the past ten years, several chromosomal loci have been identified by genome-wide association studies to influence the risk of coronary artery disease (CAD) and its risk factors. The GUCY1A3 gene encoding the α1 subunit of the soluble guanylyl cyclase (sGC) resides at one of these loci and has been strongly associated with blood pressure and CAD risk. More recently, further genes in the pathway encoding the endothelial nitric oxide synthase, the phosphodiesterases 3A and 5A, and the inositol 1,4,5-trisphosphate receptor I-associated protein (IRAG), i...
March 27, 2018: Nitric Oxide: Biology and Chemistry
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