Nitric oxide Dotaz Zobrazit nápovědu
Nitric oxide synthases (NOS) are a family of isoforms responsible for the synthesis of the potent dilator nitric oxide (NO). Expression of inducible NOS (iNOS) occurs in conditions of inflammation, and produces large amounts of NO. In pathological conditions iNOS is regarded as a harmful enzyme and is proposed to be a major contributor to diseases of the cardiovascular system such as atherosclerosis. In this review, we address the notion that iNOS is a detrimental enzyme in disease and discuss its potentially beneficial roles. Additionally, we describe other molecules associated with iNOS in diseases such as atherosclerosis, and current research on therapeutic inhibitors tested to reduced pathology associated with cardiovascular diseases (CVD).
- Klíčová slova
- COX-2, Cardiovascular diseases, Cyclooxygenase-2 (COX-2), Endothelial NOS (eNOS), Inducible NOS (iNOS), Nitric oxide synthase (NOS), Oxidative stress,
- MeSH
- kardiovaskulární nemoci metabolismus MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
The review briefly summarizes current knowledge of the bacterial nitric-oxide reductase (NOR). This membrane enzyme consists of two subunits, the smaller one contains haem C and the larger one two haems B and nonhaem iron. The protein sequence and structure of metal centres demonstrate the relationship of NOR to the family of terminal oxidases. The binuclear Fe-Fe reaction centre, consisting of antiferromagnetically coupled haem B and nonhaem iron, is analogous to Fe-Cu centre of terminal oxidases. The data on the structure and function of NOR and terminal oxidases suggest that all these enzymes are closely evolutionally related. The catalytic properties are determined most of all by the relatively high toxicity of nitric oxide as a substrate and the resulting strong need to maintain its concentration at nanomolar levels. A kinetic model of the action of the enzyme comprises substrate inhibition. NOR does not conserve the free energy of nitric oxide reduction because it does not work as a proton pump and, moreover, the protons coming into the reaction are taken from periplasm, i.e. they do not cross the membrane.
- MeSH
- Bacteria enzymologie MeSH
- oxid dusnatý metabolismus MeSH
- oxidoreduktasy chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nitric-oxide reductase MeSH Prohlížeč
- oxid dusnatý MeSH
- oxidoreduktasy MeSH
Research increasingly suggests that nitric oxide (NO) plays a role in the pathogenesis of schizophrenia. One important line of evidence comes from genetic studies, which have repeatedly detected an association between the neuronal isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the pathogenetic pathways linking nNOS, NO, and the disorder remain poorly understood. A deficit in sensorimotor gating is considered to importantly contribute to core schizophrenia symptoms such as psychotic disorganization and thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR, rs6490121 and rs41279104), associated with schizophrenia and cognition in previous studies, and tested their association with the efficiency of sensorimotor gating in healthy human adults. We found that risk variants of Ex1f-VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse inhibition (PPI) of the acoustic startle reflex, a standard measure of sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f-VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of risk alleles, being highest in participants with no risk allele, while lowest in individuals who carry three risk alleles. Our findings indicate that NO is involved in the regulation of sensorimotor gating, and highlight one possible pathogenetic mechanism for NO playing a role in the development of schizophrenia psychosis.
- Klíčová slova
- Endophenotypes, NOS1, Nitric oxide, Prepulse inhibition, Schizophrenia, Startle,
- MeSH
- dospělí MeSH
- exony MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- minisatelitní repetice MeSH
- oxid dusnatý fyziologie MeSH
- prepulsní inhibice genetika MeSH
- schizofrenie genetika MeSH
- senzorický gating genetika MeSH
- synthasa oxidu dusnatého, typ I genetika MeSH
- úleková reakce genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- NOS1 protein, human MeSH Prohlížeč
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ I MeSH
Pulmonary hypertension is a condition characterized by vasoconstriction, vascular cell proliferation, inflammation, microthrombosis, and vessel wall remodelation. Pulmonary endothelial cells produce vasoactive substances with vasoconstrictive as well as vasodilatative effects. The imbalance of these endothelium-derived vasoactive substances induced by endothelial dysfunction is very important in the pathogenesis of PH. One of most important substances with vasodilatative effect is nitric oxide. We provide a comprehensive insight into role of NO in the pathgenesis of PH and discuss perspectives and challenges in PH therapy based on NO administration.
- Klíčová slova
- NO inhalation, Nitric oxide, Nitric oxide synthase, Pathophysiology, Pulmonary hypertension, Therapy,
- MeSH
- antihypertenziva farmakologie terapeutické užití MeSH
- lidé MeSH
- oxid dusnatý metabolismus MeSH
- plicní hypertenze farmakoterapie metabolismus patofyziologie MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- vazodilatace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antihypertenziva MeSH
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ III MeSH
Leaf senescence is often associated with increased oxidative damage to cellular macromolecules by reactive oxygen species. However, very little is known about other radicals: gaseous free radical nitric oxide and related molecules--reactive nitrogen species. This review brings a short survey of the questions.
- MeSH
- dioxygenasy metabolismus MeSH
- oxid dusnatý chemie toxicita MeSH
- reaktivní formy dusíku chemie MeSH
- rostliny chemie enzymologie toxicita MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- dioxygenasy MeSH
- oxid dusnatý MeSH
- reaktivní formy dusíku MeSH
Nitric oxide (NO) emerged as a key signal molecule in plants. During the last two decades impressive progress has been made in plant NO research. This small, redox-active molecule is now known to play an important role in plant immunity, stress responses, environmental interactions, plant growth and development. To more accurately and robustly establish the full spectrum of NO bioactivity in plants, it will be essential to apply methodological best practice. In addition, there are some instances of conflicting nomenclature within the field, which would benefit from standardization. In this context, we attempt to provide some helpful guidance for best practice associated with NO research and also suggestions for the cognate terminology.
- Klíčová slova
- S-nitrosylation, fluorescence, mitochondria, nitrate reductase, nitric oxide, nitric oxide synthase,
- MeSH
- oxid dusnatý * MeSH
- rostliny * MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- oxid dusnatý * MeSH
Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the. surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways.
- MeSH
- lidé MeSH
- mechanika dýchání fyziologie MeSH
- oxid dusnatý fyziologie MeSH
- plíce metabolismus patologie MeSH
- poruchy dýchání metabolismus patologie MeSH
- synthasa oxidu dusnatého, typ II biosyntéza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- oxid dusnatý MeSH
- synthasa oxidu dusnatého, typ II MeSH
Metabolic responses of epiphytic lichen Ramalina farinacea to cadmium (Cd) and/or nitric oxide (NO) scavenger (cPTIO) were studied. Accumulation of Cd and other metallic nutrients was not affected by cPTIO while total and absorbed amounts differed. Cd-induced NO formation was suppressed by cPTIO but ROS signal was synergistically enhanced, confirming that NO is essential to keep ROS under control. This excessive ROS generation could be a reason for depleted amount of all fatty acids, including SFAs, MUFAs and PUFAs. Total content of fatty acids reached 3.89 mg/g DW in control with linoleic (40%), palmitic (24%), oleic (12.8%) and stearic (8%) acids as major compounds: interestingly, shift in relative ratio of saturated (from 40 to 35% of total FAs) versus polyunsaturated fatty acids (from 42 to 48% of total FAs) was observed. Glutathione was suppressed by all treatments but Krebs acids were almost unaffected by cPTIO, indicating no regulatory role of NO in their accumulation. On the contrary, Cd-induced elevation in NO signal was related to increase in ascorbate and proline content while cPTIO suppressed it, indicating a tight relation between NO and these metabolites. Data are compared also with algae and vascular plants to show similarities between various life lineages.
- Klíčová slova
- Antioxidants, Fluorescence microscopy, Heavy metals, Oxidative stress, Photobiont, Polyunsaturated fatty acids,
- MeSH
- fluorescenční mikroskopie MeSH
- kadmium farmakologie MeSH
- lišejníky účinky léků metabolismus MeSH
- oxid dusnatý antagonisté a inhibitory biosyntéza metabolismus MeSH
- scavengery volných radikálů farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kadmium MeSH
- oxid dusnatý MeSH
- scavengery volných radikálů MeSH
As a part of our extensive structure-activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E2 (PGE2) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.
- Klíčová slova
- Anti-inflammatory properties, Dual inhibitors, Nitric oxide, Prostaglandin E(2), Pyrimidine derivatives,
- MeSH
- dinoproston antagonisté a inhibitory MeSH
- molekulární struktura MeSH
- myši inbrední C57BL MeSH
- oxid dusnatý antagonisté a inhibitory MeSH
- pyrimidiny chemická syntéza farmakologie toxicita MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dinoproston MeSH
- oxid dusnatý MeSH
- pyrimidiny MeSH
This contribution reports the design, synthesis and photochemical properties of a novel cationic, water soluble, β-cyclodextrin (βCD) conjugate integrating an anthracene moiety and a nitroaniline derivative within the primary side of the βCD scaffold. Photoinduced energy transfer between the anthracene and the nitroaniline chromophores effectively suppresses the fluorescence of the anthracene unit. Excitation with visible light triggers the release of nitric oxide (NO) from the nitroaniline chromophore, accompanied to the concomitant revival of the anthracene fluorescence, which acts as an optical reporter for detecting the amount of the NO released. Furthermore, the anthracene moiety photogenerates singlet oxygen (1O2) sequentially to NO release. The conjugate is also able to accommodate hydrophobic guests within the βCD cavity, as proven by using naphthalene as a model compound. In view of the key role NO and 1O2 play as anticancer and antibacterial species, the present βCD derivative represents an intriguing candidate for further studies in biopharmaceutical research addressed to multimodal therapeutic applications.
- Klíčová slova
- Cyclodextrin, Fluorescence, Light, Nitric oxide, Singlet oxygen,
- MeSH
- beta-cyklodextriny chemie MeSH
- fluorescence MeSH
- hydrofobní a hydrofilní interakce MeSH
- oxid dusnatý chemie MeSH
- světlo MeSH
- systémy cílené aplikace léků * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-cyklodextriny MeSH
- oxid dusnatý MeSH