Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Short-term estrogenic regulation of neuronal nitric oxide synthase (nNOS) mRNA in the ventrolateral subdivision of the ventromedial nucleus (VLVMN), an area central to lordosis, was demonstrated using in situ hybridization. Estrogen-treated animals showed a significantly greater signal in the VLVMN, but not the arcuate or supraoptic nuclei, compared to ovariectomized controls. Neuronal NOS may be involved in early actions of estrogen in the VLVMN.
Brain Res Mol Brain Res 1998 Aug 15
PMID:Regulation of neuronal nitric oxide synthase mRNA in lordosis-relevant neurons of the ventromedial hypothalamus following short-term estrogen treatment. 972 9

Hereditary argininemia manifests as neurological disturbance and mental retardation, features not observed in other amino acidemias. The cytotoxic effect of a high concentration of L-arginine (L-Arg) was investigated using NB9 human neuroblastoma cells (NB9), which express neuronal nitric oxide synthase (nNOS). When the concentration of L-Arg in the medium increased from 50 microM to 2 mM after incubation for 48 hr, the intracellular concentration of L-Arg increased from 68.0 +/- 1 pmol/10(6) cells to 1310.0 +/- 5 pmol/10(6) cells and that of L-citrulline (L-Cit) from undetectable levels to 47.1 +/- 0.2 pmol/10(6) cells (mean +/- SD of three independent analyses). This increase in intracellular L-Arg levels caused a decrease in NOS activity by approximately 71%. Flow cytometric analysis showed that reactive oxygen species (ROS) are produced in NB9 exposed to 2 mM L-Arg. The production of ROS was abolished by a NOS inhibitor, NG-nitro-L arginine-methylester. Production of ROS was also observed when NB9 were treated with L-Cit for 48 hr. To investigate the effect of L-Cit on the activity of NOS, a kinetic study on nNOS was conducted using cellular extracts from NB9. The apparent Km value of nNOS for L-Arg was 8.4 microM, with a Vmax value of 8.2 pmol/min/mg protein. L-Cit competitively inhibited NOS activity, as indicated by an apparent Ki value of 65 nM. These results suggest that L-Cit formed by nNOS in L-Arg-loaded neuronal cells inhibits NOS activity and nNOS in these L-Arg-loaded cells functions as a NADPH oxidase to produce ROS, which may cause neurotoxicity in argininemia.
Mol Med 1998 Aug
PMID:High concentration of L-arginine suppresses nitric oxide synthase activity and produces reactive oxygen species in NB9 human neuroblastoma cells. 974 7

Nitric oxide (NO), derived from L-arginine by the action of nitric oxide synthase (NOS), is a mediator of many diverse biological activities, including vasodilation, neurotransmission and inhibition of platelet adhesion. A role for NO in the maintenance of rat and rabbit pregnancy is supported by a variety of studies. A recent study in women demonstrated that myometrial inducible NOS (iNOS) expression was greater in the early third trimester than either the late third trimester or in the non-pregnant condition, suggesting that increased iNOS expression is involved in the maintenance of human pregnancy. Constitutive NOS (cNOS) expression was not determined. The aim of this study was to compare constitutive NOS (both eNOS and bNOS) expression in the human non-pregnant uterus, preterm pregnant uterus (25-34 weeks gestation) and term pregnant uterus (>37 weeks gestation) using immunohistochemistry and Western blotting. Preterm pregnant samples were taken from women with a variety of pathologies necessitating early delivery. We found that eNOS and bNOS protein concentrations were greater in the preterm pregnant myometrium than non-pregnant myometrium. eNOS, but not bNOS, protein concentration was lower in myometrial samples obtained at term compared with those obtained preterm. We conclude that the constitutive isoforms of NOS are also up-regulated in human pregnancy and may play a role in the maintenance of myometrial quiescence.
Mol Hum Reprod 1999 Feb
PMID:Myometrial constitutive nitric oxide synthase expression is increased during human pregnancy. 1006 74

Recent reports indicate an association between second trimester human influenza viral infection and later development of schizophrenia. Postmortem human brain studies also provide evidence for reduction in Reelin mRNA (an important secretory protein responsible for normal lamination of the brain) in schizophrenic brains. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of reelin in day 0 neonatal brains. Prenatally-infected murine brains from postnatal day 0 showed significant reductions in reelin-positive cell counts in layer I of neocortex and other cortical and hippocampal layers when compared to controls. Whereas layer I Cajal-Retzius cells produced significantly less Reelin in infected animals, the same cells showed normal production of calretinin and nNOS when compared to control brains. Moreover, prenatal viral infection caused decreases in neocortical and hippocampal thickness. These results implicate a potential role of prenatal viral infection in causation of neuronal migration abnormalities via reduction in Reelin production in neonatal brains.
Mol Psychiatry 1999 Mar
PMID:Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. 1020 46

There is contradictory information on the relevance of nitric oxide (NO) and cGMP for the function of brain capillary endothelial cells (BCEC) forming the blood-brain barrier (BBB). Therefore, NO/cGMP-mediated signal transduction was investigated in cell cultures of BCEC and of astrocytes (AC) inducing BBB properties in BCEC. Constitutive, Ca2+-activated isoforms of NO synthase (NOS) were found in BCEC (endothelial NOS: eNOS) and in AC (neuronal NOS: nNOS), leading to increased NO release after incubation with the Ca2+-ionophore A23187. Both cell types expressed inducible NOS (iNOS) after incubation with cytokines. Soluble guanylate cyclase (sGC) was detected in both cell types. NO-dependent cGMP formation were observed in BCEC and, less pronounced, in AC. Furthermore, both cell types formed cGMP independently of NO via stimulation of particulate guanylate cyclase (pGC). cGMP-dependent protein kinase (PKG) type Ibeta, but not type II, was expressed in BCEC and AC. In BCEC, vasodilator-stimulated phosphoprotein (VASP) was detected, an established substrate of PKG and associated with microfilaments and cell-cell contacts. Phosphorylation of VASP was intensified by increased intracellular cGMP concentrations. The results indicate that BCEC and, to a smaller degree, AC can form NO and cGMP in response to different stimuli. In BCEC, NO/cGMP-dependent phosphorylation of VASP is demonstrated, thus providing a possibility of influencing cell-cell contacts.
Brain Res Mol Brain Res 1999 Apr 20
PMID:Phosphorylation of vasodilator-stimulated phosphoprotein: a consequence of nitric oxide- and cGMP-mediated signal transduction in brain capillary endothelial cells and astrocytes. 1021 24

The peri-implantation period is a critical time during murine development. Although the importance of nitric oxide has been demonstrated during gestation, its role in implantation has not been fully defined. The aim of this study was to quantify (by Western blotting) two prominent nitric oxide synthase (NOS) isoforms, inducible (iNOS) and endothelial (eNOS) and localize all three forms [iNOS, eNOS, and neuronal (nNOS)] by immunohistochemistry in uterine tissue from days 4 through 8 of pregnancy. By day 6, iNOS values were significantly elevated in implantation sites compared with interimplantation regions and continued to rise through day 8. Analysis of eNOS was similar, but implantation site values peaked by days 6 and 7. Labelled iNOS cells were within the decidua, around myometrial vessels, and within the ectoplacental cone. At implantation, eNOS was conspicuous, displaying label adjacent to the embryo in vessels of the primary decidual zone. nNOS was localized mainly in the mesometrium and myometrium and did not appear to change throughout the peri-implantation period. The increased iNOS and eNOS values following implantation in the embryonic site may imply roles in tissue remodelling, immunosuppression and vasoregulation. Nitric oxide may play an important role in the mechanisms of implantation where these factors are keys to successful pregnancy.
Mol Hum Reprod 1999 May
PMID:Nitric oxide synthase distribution during implantation in the mouse. 1033 70

Glutamate excitotoxicity, oxidative stress, and mitochondrial dysfunctions are common features leading to neuronal death in cerebral ischemia, traumatic brain injury, Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nitric oxide (NO) alone or in cooperation with superoxide anion and peroxynitrite is emerging as a predominant effector of neurodegeneration The use of NO synthase (NOS) inhibitors and mutant mice lacking each NOS isoform have provided evidence for the injurious effects of NO derived from neuronal or inducible isoforms. New neuroprotective strategies have been proposed with selective NOS inhibitors for the neuronal (ARL17477) or the inducible (1400 W) isoforms or with compounds combining in one molecule selective nNOS inhibition and antioxidant properties (BN 80933), in experimental ischemia-induced acute neuronal damage. The efficacy of these new strategies is well established in acute neuronal injury but remains to be determined in more chronic neurological diseases.
Cell Mol Life Sci 1999 Jul
PMID:Nitric oxide synthases: targets for therapeutic strategies in neurological diseases. 1044 86

Duchenne muscular dystrophy is a devastating neuromuscular disease caused by lack of the protein, dystrophin, in skeletal muscle and heart, although the biochemical mechanism by which dystrophin loss causes muscle dysfunction is unknown. Here we show that the dystrophin-deficient mdx mouse and a mouse lacking both dystrophin and the dystrophin-related protein, utrophin (dko), have abnormal electrocardiograms (ECGs). In skeletal muscle, dystrophin is normally associated with neuronal nitric oxide synthase (nNOS) at the sarcolemma. Consequently, we have measured NOS isoform activities in hearts from control, mdx and dko mice. In control mouse hearts, eNOS and nNOS activities increased by 120% and 47%, respectively, between 2 and 6 months of age. In mdx mice, myocardial nNOS activity was decreased by 60%, 84% and 80% at 2, 6 and 12 months of age, respectively. Similarly, hearts from dko mice showed a 65% decrease in nNOS activity compared to controls at 2 months of age. Endothelial NOS (eNOS) activity was not affected by dystrophin loss, but inducible NOS (iNOS) activity was seven-fold higher than control in the mdx mouse heart by 12 months of age. We conclude that lack of dystrophin in the mdx mouse results in abnormal ECGs that are associated with decreased myocardial nNOS and increased iNOS activities.
J Mol Cell Cardiol 1999 Oct
PMID:Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of Duchenne muscular dystrophy. 1052 23

The second PDZ domain of postsynaptic density-95 (PSD-95 PDZ2) plays a critical role in coupling N-methyl-D-aspartate receptors to neuronal nitric oxide synthase (nNOS). In this work, the solution structure of PSD-95 PDZ2 was determined to high resolution by NMR spectroscopy. The structure of PSD-95 PDZ2 was compared in detail with that of alpha1-syntrophin PDZ domain, as the PDZ domains share similar target interaction properties. The interaction of the PSD-95 PDZ2 with a carboxyl-terminal peptide derived from a cytoplasmic protein CAPON was studied by NMR titration experiments. Complex formation between PSD-95 PDZ2 and the nNOS PDZ was modelled on the basis of the crystal structure of the alpha1-syntrophin PDZ/nNOS PDZ dimer. We found that the prolonged loop connecting the betaB and betaC strands of PSD-95 PDZ2 is likely to play a role in both the binding of the carboxyl-terminal peptide and the nNOS beta-finger. Finally, the backbone dynamics of the PSD-95 PDZ2 in the absence of bound peptide were studied using a model-free approach. The "GLGF"-loop and the loop connecting alphaB and betaF of the protein display some degree of flexibility in solution. The rest of the protein is rigid and lacks detectable slow time-scale (microseconds to milliseconds) motions. In particular, the loop connecting betaB and betaC loop adopts a well-defined, rigid structure in solution. It appears that the loop adopts a pre-aligned conformation for the PDZ domain to interact with its targets.
J Mol Biol 2000 Jan 14
PMID:Solution structure and backbone dynamics of the second PDZ domain of postsynaptic density-95. 1062 22

Controversy surrounds the involvement of nitric oxide (NO) in myocardial ischaemia-reperfusion injury and the balance between deleterious and beneficial effects. NO synthase (NOS) is expressed constitutively as two isoforms: endothelial (eNOS) and neuronal (nNOS). Knockout mice lacking the gene for either eNOS (eNOS KO) or nNOS (nNOS KO), were compared with wild-types (WT) during a protocol of global ischaemia-reperfusion injury. Thirty-six mouse hearts (12 from each group) were isolated and the aorta cannulated for Langendorff perfusion with modified Krebs solution at constant pressure. An apical suture connected the left ventricle to a force transducer via a light weight coupling rod. Following stabilization hearts were subjected to 30 min of global ischaemia at 37 degrees C. During 30 min reperfusion, the recovery of baseline force-rate product (F%) was recorded. Hearts were then stained with tetrazolium, frozen, sliced, and fixed with formalin. Slices were compressed between plexiglas plates, and a magnified video image digitized to allow planimetry for infarct size (as percentage of ventricular volume I/R). Although recovery of contractile function did not differ between groups, eNOS KOs suffered significantly larger infarcts than WT or nNOS KOs (41 v 33 and 30% respectively, P<0.05 for both comparisons). A protective role for eNOS against global ischaemia-reperfusion injury has been demonstrated for the first time in murine myocardium. This may have important clinical implications for future pharmacotherapy to enhance myocardial protection.
J Mol Cell Cardiol 2000 Jan
PMID:Infarct size and nitric oxide synthase in murine myocardium. 1065 88


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