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malfunction
attachment of N-glycan to the Asn695 residue inhibits activity by disturbing electron transfer. N-glycosylated iNOS consumes NADPH more slowly than the unliganded enzyme. Mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
malfunction
inhibition of NOS function by NOS inhibitor L-NG-monomethyl arginine (L-NMMA) results in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during dental papilla cell (DPC) differentiation
malfunction
role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia (PE), multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. PE pathophysiology can result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/ reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide, which produces peroxynitrite ONOO-, a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS posttranslational modifications (for instance by S-glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating superoxide, thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS can be posttranslationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. Analysis of the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis, detailed overview. Oxidative stress is thought to play a pivotal role in the decreased NO bioavailability in PE pathophysiology, via several mechanisms including an inhibition of eNOS (eNOS uncoupling) and subsequent defect of NO biosynthesis, or through the formation of peroxynitrite, via the reaction of NO with the radical anion superoxide. eNOS inhibition is associated with a decrease in endothelial-dependent relaxation in vitro and in vivo. Therapeutic perspectives targeting oxidative stress and NO/eNOS dysfunction
malfunction
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attachment of N-glycan to the Asn695 residue inhibits activity by disturbing electron transfer. N-glycosylated iNOS consumes NADPH more slowly than the unliganded enzyme. Mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
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malfunction
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inhibition of NOS function by NOS inhibitor L-NG-monomethyl arginine (L-NMMA) results in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during dental papilla cell (DPC) differentiation
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metabolism
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activation of G protein-coupled estrogen receptor in the supraoptic and paraventricular nuclei of the hypothalamus inhibits the phosphorylation of ERK 1/2, which induces a decrease in NADPH-diaphorase expression
metabolism
synthesis of the signaling molecule nitric oxide
metabolism
the enzyme plays an important role in host defense system by catalyzing the production of nitric oxide
physiological function
eNOS selectively activates N-Ras but not K-Ras on the Golgi complex of T cells engaged with antigen-presenting cells by S-nitrosylation at Cys118
physiological function
si-RNA mediated knockdown of eNOS leads to a striking increase in AMP-activated protein kinase phosphorylation, homozygot eNOS knockout mice show a marked increase in AMP-activated protein kinase phosphorylation in liver and lung compared to wild type mice
physiological function
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the brain neuronal NOS and inducible NOS are respectively involved in the bombesin-induced secretion of noradrenaline and adrenaline from the adrenal medulla
physiological function
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developmental but not adult exposure to polychlorinated biphenyls significantly reduces NO synthase responses to hyperosmolality in neuroendocrine cells. Reduced NADPH diaphorase activity produced by in utero exposure persists in stimulated late adult rats concomitant with reduced osmoregulatory capacity
physiological function
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during muscle pain development, a significant contralateral increase in the number of NADPH-diaphorase reactive cells is accompanied by anipsilateral increase in c-Fos expression in lamina VII. NADPH-diaphorase reactive neurons of the contralateral ventral horn may be involved through commissural connections in the maintenance of the neuronal activity associated with acute muscle inflammation. During acute myositis, plastic changes in the ventral horn may activate the processes of disinhibition due to an increase in the number of NADPH-diaphorase reactive neurons in the spinal gray matter
physiological function
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estradiol regulates the nitrergic system in the supraoptic and paraventricular hypothalamic nuclei under acute osmotic stress conditions, but the effects specifically depend on the anatomical subregions and different estrogen receptors. The inhibition of estrogen receptor alpha enhances the effect of 1.5 M NaCl injection, inducing a further decrease in the number of NADPH-diaphorase-positive cells. The estrogen receptor beta agonist enhances and the estrogen receptor beta antagonist blocks the effect of NaCl injection on the number of NADPH-diaphorase-positive neurons in the supraoptic hypothalamic nuclei and in the medial magnocellular subdivision of the paraventricular hypothalamic nuclei
physiological function
endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis
physiological function
NADPH oxidases (NOX2/NOX4) and inducible nitric oxide synthase (iNOS) derived oxidative stress play a key role in psoriasis induced kidney dysfunction. NADPH oxidase (NOX2 and NOX4) isoforms, and inducible nitric oxidase synthase (iNOS) are elevated in the renal tissue under inflammatory conditions such as acute kidney injury and chronic kidney disease. These enzymes are capable of producing reactive oxygen species (ROS) in large quantities under inflammatory conditions, which may cause oxidative damage to biological macromolecules such as lipids, proteins and nucleic acids leading to malfunction of cellular structures through dysregulation of ion pumps, and enzymatic activity
physiological function
nitric-oxide synthase (NOS) is required in mammals to generate nitric-oxide for regulating blood pressure, synaptic response, and immune defense
physiological function
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the product nitric oxide may function as a co-transmitter in the central nervous system of Helix pomatia
physiological function
the product nitric oxide may function as a co-transmitter in the central nervous system of Helix pomatia
physiological function
in endothelium and placenta, NO is biosynthesized by the endothelial nitric oxide synthase (eNOS), and confers to endothelium its vasorelaxing and anti-aggregant properties. NO participates to placentation and the synthesis of the vascular endothelial growth factor (VEGF). NO plays an essential role in vascular homeostasis due to its vasodilatory effect. NO is synthesized by nitric oxide synthases (NOS), from L-arginine and molecular oxygen (O2). In short, the reaction allowing NO synthesis can be compared to two monooxygenation reactions. The first reaction consists of the oxidation of L-arginine. This reaction produces an intermediate, -OH-L-arginine, which is rapidly oxidized into L-citrulline. These two oxygenation reactions occur in parallel with a concomitant conversion of NADPH to NADP+. The electrons are supplied by NADPH, transferred to flavins (FAD and FMN) and calmodulin, then presented to heme, the catalytic center. Three NOS isoforms have been characterized, the neuronal NOS (nNOS or NOS1), the inducible NOS (iNOS or NOS2) and the endothelial NOS (eNOS or NOS3). NO released by endothelial cells in vivo causes a permanent vasodilation of the arterial tone that helps to regulate arterial pressure. During pregnancy, NO has a primary role in vasodilation and blood pressure regulation, placentation and VEGF synthesis. Oxidative stress impact on NO bioavailability, detailed overview. S-Glutathionylation can be promoted by NO, via mechanisms implicating S-nitrosoglutathione (GSNO) and thiyl radicals. S-glutathionylated proteins reversibly accumulate under oxidative stress conditions and can be rapidly reduced by reducing agents and glutaredoxins. S-glutathionylation alters the structure, folding and function of proteins, and can be considered as an adaptative and protective mechanism against the irreversible oxidation of cysteine residues during oxidative stress
physiological function
inducible nitric oxide synthase (iNOS) is a key inflammatory factor. It functions in both acute and chronic inflammation. Nitric oxide (NO) is a signaling mediator with many diverse and often contradictory biological activities. In mammals, NO is produced by a family of nitric oxide synthase (NOS). The NOS family includes neuronal nitric oxide synthase (nNOS, type I), inducible nitric oxide synthase (iNOS, type II), and endothelial nitric oxide synthase (eNOS, type III). All these three NOS isoforms catalyze a similar reaction. Consuming NADPH and O2, NOS oxidizes L-arginine into L-citrulline and releases NO. The reaction is an oxidation-reduction reaction, and electron transfer plays a vital role. Inducible nitric oxide synthase (iNOS) plays critical roles in the inflammatory response and host defense. The essence of nitric oxide synthase catalytic reaction is an electron transfer process, which involves a series of conformational changes, and the linker between the flavin mononucleotide-binding domain and the flavin adenine dinucleotide-binding domain plays vital roles in the conformational changes. Residue Asn695 is part of the linker. Enzyme iNOS is N-glycosylated at its Asn695 residue and N-glycosylation of Asn695 might suppress iNOS activity by disturbing electron transfer
physiological function
leptin-induced NO production in tanycytes may affect the neurogenesis occurs in the hypothalamus. The increased NADPH-d staining in both the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the leptin-treated rats suggests that both the PVN and ARC may be important centers in the hypothalamus for the leptin action, mediated at least in part by increased NO synthesis. The present observations also suggest that leptin may activate NOS thereby resulting in increased production of NO in hypothalamic tanycytes, possibly affecting the release of neurohormones and hypothalamic neurogenesis
physiological function
nitrergic neurons in the rat stomach supply the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the astric wall. A small number of fibres are in the mucosa. All the neurons appear to have a single axon and in most cases a type I morphology. Type I is the typical morphology of enteric motor neurons that supply the muscle of the gastrointestinal tract. Neuronal nitric oxide synthase (nNOS) neurons do not supply terminals around myenteric nerve cells, whether NADPHd histochemistry or nNOS immunohistochemistry is used to locate the terminals of nNOS neurons. Thus, nNOS appears to be exclusively in motor neurons supplying the muscle of the rat stomach. This may be different from other species. nNOS immunoreactivity identifies 4 classes of motor neurons that supply the muscle of the rat stomach, an analysis of cell body sizes does not identify separate grouping of neurons. The rat stomach harbours large numbers of nNOS neurons, all or almost all of which are motor neurons supplying the external muscle, the muscularis mucosae and intramural arteries
physiological function
nitric oxide (NO) is a key cellular signaling mediator involved in the overall regulation of physiological homeostasis and in numerous pathological processes related to cardiovascular, nervous and immune systems. NO is formed together with L-citruline by nitric-oxide synthases (NOS) that catalyze the oxidation of L-arginine using nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), tetrahydrobiopterin (BH4) and O2 as cofactors. The overall catalytic process is driven by reducing equivalents supplied by NADPH. NOS are composed of a reductase domain which binds NADPH and the two flavins and an oxygenase domain which binds the heme, L-arginine, BH4 and O2. These two domains are connected by the calmodulin-binding domain. The electron flow leading to the formation of NO is initiated by the binding of NADPH to the reductase domain and requires the binding of calmodulin for efficient FMN to heme electron transfer. NO is produced by three NOS isoforms, the two first are constitutive, neuronal (nNOS) and endothelial (eNOS) whereas the third one is inducible (iNOS). Efficient photoactivatable NADPH analogues targeting NOS can have important implications for generating apoptosis in tumor cells or modulating NO-dependent physiological processes
physiological function
nitric oxide (NO) is a ubiquitous gaseous cellular messenger with multiple physiological roles in the brain, such as synaptic plasticity, neurotransmission, neuronal communication, neurogenesis, learning, and memory. NO can be generated by three different isoforms of the enzyme nitric oxide synthase (NOS): neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), from L-arginine as the substrate and molecular oxygen and NADPH as cosubstrates
physiological function
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nitric oxide (NO) is synthesized from L-arginine by the NADPH-dependent enzyme nitric oxide synthase (NOS), and is involved in many essential biological functions including immune defense, vascular regulation, muscle relaxation, and neuromodulation, and neurotransmission
physiological function
nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation, role of nitric oxide in odontoblastic differentiation of rat dental papilla cells, overview. NO regulates the odontoblastic differentiation of dental papilla cells (DPCs), thereby influencing dentin formation and tooth development. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) promotes the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression are elevated by SNAP at low concentrations and suppressed at high concentration. Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) abolishes the positive influence of SNAP on the odontoblastic differentiation of DPCs
physiological function
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nitrergic neurons in the rat stomach supply the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the astric wall. A small number of fibres are in the mucosa. All the neurons appear to have a single axon and in most cases a type I morphology. Type I is the typical morphology of enteric motor neurons that supply the muscle of the gastrointestinal tract. Neuronal nitric oxide synthase (nNOS) neurons do not supply terminals around myenteric nerve cells, whether NADPHd histochemistry or nNOS immunohistochemistry is used to locate the terminals of nNOS neurons. Thus, nNOS appears to be exclusively in motor neurons supplying the muscle of the rat stomach. This may be different from other species. nNOS immunoreactivity identifies 4 classes of motor neurons that supply the muscle of the rat stomach, an analysis of cell body sizes does not identify separate grouping of neurons. The rat stomach harbours large numbers of nNOS neurons, all or almost all of which are motor neurons supplying the external muscle, the muscularis mucosae and intramural arteries
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physiological function
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inducible nitric oxide synthase (iNOS) is a key inflammatory factor. It functions in both acute and chronic inflammation. Nitric oxide (NO) is a signaling mediator with many diverse and often contradictory biological activities. In mammals, NO is produced by a family of nitric oxide synthase (NOS). The NOS family includes neuronal nitric oxide synthase (nNOS, type I), inducible nitric oxide synthase (iNOS, type II), and endothelial nitric oxide synthase (eNOS, type III). All these three NOS isoforms catalyze a similar reaction. Consuming NADPH and O2, NOS oxidizes L-arginine into L-citrulline and releases NO. The reaction is an oxidation-reduction reaction, and electron transfer plays a vital role. Inducible nitric oxide synthase (iNOS) plays critical roles in the inflammatory response and host defense. The essence of nitric oxide synthase catalytic reaction is an electron transfer process, which involves a series of conformational changes, and the linker between the flavin mononucleotide-binding domain and the flavin adenine dinucleotide-binding domain plays vital roles in the conformational changes. Residue Asn695 is part of the linker. Enzyme iNOS is N-glycosylated at its Asn695 residue and N-glycosylation of Asn695 might suppress iNOS activity by disturbing electron transfer
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physiological function
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leptin-induced NO production in tanycytes may affect the neurogenesis occurs in the hypothalamus. The increased NADPH-d staining in both the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the leptin-treated rats suggests that both the PVN and ARC may be important centers in the hypothalamus for the leptin action, mediated at least in part by increased NO synthesis. The present observations also suggest that leptin may activate NOS thereby resulting in increased production of NO in hypothalamic tanycytes, possibly affecting the release of neurohormones and hypothalamic neurogenesis
-
physiological function
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nitric oxide (NO) is a ubiquitous gaseous cellular messenger with multiple physiological roles in the brain, such as synaptic plasticity, neurotransmission, neuronal communication, neurogenesis, learning, and memory. NO can be generated by three different isoforms of the enzyme nitric oxide synthase (NOS): neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), from L-arginine as the substrate and molecular oxygen and NADPH as cosubstrates
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physiological function
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nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation, role of nitric oxide in odontoblastic differentiation of rat dental papilla cells, overview. NO regulates the odontoblastic differentiation of dental papilla cells (DPCs), thereby influencing dentin formation and tooth development. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) promotes the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression are elevated by SNAP at low concentrations and suppressed at high concentration. Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) abolishes the positive influence of SNAP on the odontoblastic differentiation of DPCs
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additional information
residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
additional information
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residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
additional information
the large numbers of nNOS neurons and the density of innervation of the circular muscle and pyloric sphincter suggest that there is a finely graded control of motor function in the stomach by the recruitment of different numbers of inhibitory motor neurons
additional information
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the large numbers of nNOS neurons and the density of innervation of the circular muscle and pyloric sphincter suggest that there is a finely graded control of motor function in the stomach by the recruitment of different numbers of inhibitory motor neurons
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additional information
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residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
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