UNIPROT:P50583 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inducible human cationic amino acid transporter hCAT-2B was expressed in Xenopus laevis oocytes, and this system was used to test the effect of several NO synthase (NOS) inhibitors and/or L-arginine analogues on L-arginine transport by this y+ carrier. L-NG-Methyl-L-arginine (L-NMA), asymmetrical L-NG, NG-dimethyl-L-arginine (L-ADMA), L-N5-(1-iminoethyl)-ornithine (L-NIO), L-NG-nitro-L-arginine (L-NNA), and L-NG-nitro-L-arginine methyl ester (L-NAME) all inhibited the inducible NOS II extracted from RAW 264.7 macrophages induced with bacterial lipopolysaccharide. L-NMA, L-ADMA, and L-NIO also competed with L-arginine for transport by hCAT-2B, whereas L-NNA and L-NAME did not. The two L-arginine analogues, symmetrical NG, NG-dimethyl-L-arginine (L-SDMA) and alpha-amino-delta-isothioureidovaleric acid (AITV), as well as L-lysine, did not block enzymatic activity of NOS II, but did compete for L-arginine transport mediated by hCAT-2B. L-Lysine and L-SDMA were transported efficiently by hCAT-2B and exchanged against intracellular L-arginine, resulting in an L-arginine depletion of the cells. AITV was a much poorer substrate of hCAT-2B and had only little effect on intracellular L-arginine concentrations. These data indicate that substrate recognition differs markedly between the inducible L-arginine transporter hCAT-2B and the inducible NOS II, with different L-arginine analogues having affinity to only one or both of these proteins.
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PMID:Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B. 970 Oct 46

In the adult frog, structural asymmetry of the left dorsal habenula in respect to the right counterpart has been repeatedly documented in previous studies. In the present investigation, histochemical expression of beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was examined in the habenulae of the developing and adult Rana esculenta. In tadpoles and during metamorphosis, selective neuropil staining was consistently found within a lateral compartment of the medial subnucleus of the left dorsal habenula. The staining was still present in the same location, but much less intense, in the mature frog, indicating that the neurochemical pattern observed during development was at least in part transient. Thus, the present data point out a peculiar neurochemical pattern of the habenular asymmetry in the frog, suggesting that nitric oxide may be involved in the developmental shaping which leads to an asymmetrical configuration of the habenulae. In addition, NADPH-diaphorase-positive cells were detected in the frontal organ (the extracranial component of the pineal complex in strict relationship with the habenulae in the frog), and labeled fibers were found in the frontal nerve, which arises from the frontal organ. This latter finding supports the postulated relationship of the habenular asymmetry with the occurrence of the frontal organ. The finding of NADPH-diaphorase histochemical reactivity confined to a distinct portion of the medial subnucleus of the left dorsal habenula prompted a reexamination of the cytoarchitecture of the developing and mature habenular complex in the frog. The bicompartmentalization detected with histochemistry in the medial subnucleus of the left dorsal habenula of the developing and adult frog was fully supported by the study of Nissl-stained epithalamic sections. These data point out that the left-right structural differences of the frog habenular complex are more complex than previously believed, and may be subserved by chemically regulated developmental processes.
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PMID:Nitric oxide synthase activity reveals an asymmetrical organization of the frog habenulae during development: A histochemical and cytoarchitectonic study from tadpoles to the mature Rana esculenta, with notes on the pineal complex. 1041 78

Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines, bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane interaction can induce production of these mediators. HD can also induce changes of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of this study was to investigate the effect of HD, using cuprophane (C, polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha), bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was similar with the three membranes. Cuprophane HD induced a significant increase in i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No changes were found in PAN and SPAN HD. The TNF-alpha values increased significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes of bradykinin concentration were found during HD. A significant decrease of ADA and nitrate levels was observed during HD with three membranes. No significant correlation was found between percentage increase in i-NOS activity and the changes in other parameters. These findings suggest that HD with bioincompatible membranes can induce activation of cellular i-NOS.
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PMID:[L-arginine-nitric oxide pathway in hemodialysis]. 1091 3

Hyperhomocyst(e)inaemia is associated with endothelial dysfunction in animals and humans. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inaemia are poorly understood, but may involve impaired bioavailability of endothelium-derived nitric oxide (NO). We hypothesized that acute elevation of homocyst(e)ine by oral methionine loading may stimulate the formation of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, due to a transmethylation reaction during the formation of homocyst(e)ine from methionine. We studied nine healthy human subjects (five males, four females) aged 29+/-2 years. Flow-mediated vasodilation (FMD) in the brachial artery (endothelium-dependent) and vasodilation induced by nitroglycerine (endothelium-independent) were measured with high-resolution ultrasound before and 8 h after oral methionine (100 mg/kg in cranberry juice) or placebo (cranberry juice), on separate days and in random order. Plasma homocyst(e)ine and ADMA concentrations were measured by specific HPLC methods. After a methionine bolus, elevation of homocyst(e)ine (28.4+/-3.5 micromol/l) was associated with an increased plasma concentration of ADMA (2.03+/-0.18 micromol/l) and reduced FMD (1.54+/-0.92%). Placebo had no effect on these parameters. There was a significant inverse linear relationship between ADMA concentration and FMD (r=-0.49; P<0.05), which was stronger than the relationship between the homocyst(e)ine concentration and FMD (r=-0.36; not significant). We conclude that acute elevation of the homocyst(e)ine concentration impairs vascular endothelial function by a mechanism in which an elevated concentration of ADMA may be involved. This finding may have importance for understanding the mechanism(s) leading to homocyst(e)ine-associated vascular disease, and its potential treatment.
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PMID:Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. 1117 Dec 84

To investigate the significance of nitric oxide (NO) -mediated neuron death in aging and Alzheimer's disease (AD), the concentration of asymmetrical dimethylarginine (ADMA), an endogenous NO synthase inhibitor, in the cerebrospinal fluid was determined in neurologically normal controls and patients with AD. The ADMA concentration significantly decreased with age, whereas the arginine concentration was unaltered. In patients with AD, the ADMA concentration was significantly decreased, compared with controls of a similar age (-48%, P=0.0001), and it significantly decreased with decreasing cognitive functions (r(s)=0.58, P<0.05), whereas the arginine concentration did not change. These findings suggest that ADMA may play an important role in regulating NO synthesis in brain aging and AD.
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PMID:Reduction in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in the cerebrospinal fluid during aging and in patients with Alzheimer's disease. 1160 39

The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mice. The purpose of the present work was to study the relationship between plasma tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and nitric oxide synthase (NOS) and brain lateralization. In the study, paw preference test was used to select right-pawed, left-pawed and ambidextrous mice. Mice were classified as the right-pawed if the right paw entry (RPE) score was equal to or greater than 30 (30-50), as the left-pawed if the score was equal to or less than 20 (0-20), and as the ambidextrous if the score was between 21 and 29. One week after the paw preference testing, the animals were injected intraperitoneally with either sterilized 0.9% saline or lipopolysaccharide (LPS) (5 microg/0.5 ml NS) and were killed 2 h later. Plasma was collected from each mouse. The level of plasma TNF-alpha was measured with ELISA kits provided by ENDOGEN. NO and NOS levels of plasma were detected with kits from Juli Biotechnology Company. The results showed that (1) in the normal mice, ambidextrous mice had higher NO levels compared with left-pawed mice (P<0.05). After the injection of LPS, plasma level of TNF-alpha was lower in left-pawed mice compared with those of the right-pawed and ambidextrous mice; plasma level of NO was higher in ambidextrous mice compared with those of the right- (P<0.01) and left-pawed (P<0.05) ones, and there was no significant difference in the plasma levels of NOS among ambidextrous, right- and left-pawed mice. (2) Immune parameters were correlated with the RPE scores. The shape of the curve describing this relation was similar to a parabola. In general, the levels of TNF-alpha, NO, NOS rose along with the increase of RPE if the scores were in the score range of left-pawed mice.After that, they reached a peak if the scores were in the score range of ambidextrous mice. Then they declined along with the increase of RPE if the scores were in the score range of right-pawed mice. In conclusion, plasma levels of TNF-alpha, NO and NOS were associated with brain lateralization, suggesting that the activities of Mo/Mphi were influenced by brain lateralization, and that the immune parameters were correlated with the RPE scores.
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PMID:[The correlations between plasma TNF-alpha, NO, NOS levels and brain lateralization in mice]. 1250 25

The incidence of erectile dysfunction increases with diabetes, hypertension, hypercholesterolaemia, cardiovascular disease and renal failure. All these conditions are associated with endothelial dysfunction. This review addresses the pathophysiology of erectile dysfunction with a special focus on new insights into nitric oxide (NO)-mediated pathways, oxidative stress and parallels to endothelial dysfunction. NO appears to be the key mediator promoting endothelium-derived vasodilation and penile erection. The possibility is discussed that elevated plasma concentrations of asymmetrical dimethylarginine (ADMA), an endogenous NO synthase inhibitor, may provide an additional pathomechanism for various forms of erectile dysfunction associated with cardiovascular risk factors and disease. Likewise, the role of endothelium-derived factors mediating NO-independent pathways is evaluated.
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PMID:The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. 1255 45

Development of multiple organ failure is the most complex problem in critically ill patients, and is associated with a high mortality. Asymmetrical dimethylarginine (ADMA) is an endogenously produced inhibitor of nitric oxide synthase, of which the clinical importance is currently being revealed. In Nijveldt et al. (The liver is an important organ in the metabolism of asymmetrical dimethylargenine (ADMA) Clin Nutr 2003; 22: 17-22) we showed that plasma ADMA concentration is elevated in critically ill patients and significantly related to hepatic function. Moreover, plasma ADMA concentration emerged as a strong and independent risk factor for ICU mortality in these patients. Here, we hypothesize that accumulation of ADMA is a causative factor in the development of multiple organ failure by interfering with important physiological functions of nitric oxide production.
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PMID:The asymmetrical dimethylarginine (ADMA)-multiple organ failure hypothesis. 1255 57

Oestrogen replacement therapy (ERT) has been shown to lead to favourable changes in the cardiovascular risk profile of postmenopausal women. Part of this effect is ascribed to increased production or bioavailability of nitric oxide (NO). We have tested the hypothesis that ERT lowers plasma levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of NO synthase (NOS). In a randomized double-blind study design, 40 hysterectomized postmenopausal women received conjugated equine oestrogen (CEE; 0.625 mg/day; n =14), the selective oestrogen receptor modulator raloxifene (150 mg/day; n =13) or placebo ( n =13). At baseline and after 6, 12 and 24 months of treatment, plasma was analysed for levels of arginine, ADMA, and symmetrical dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit NOS. An overall treatment effect on ADMA levels was observed in the CEE group ( P =0.004 compared with placebo), but not in the raloxifene group ( P =0.50). The decrease of ADMA levels by CEE treatment was consistent over the 2-year study period, without significant differences between the effects at 6, 12 and 24 months. The average post-baseline change in ADMA in the CEE group compared with placebo was -7.8% (95% confidence interval -12.8% to -2.9%; P =0.003). Arginine or SDMA levels did not change during treatment in any of the groups. Thus ERT with oral conjugated oestrogen, but not with raloxifene, significantly reduced plasma concentrations of the cardiovascular risk factor ADMA in healthy postmenopausal women.
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PMID:Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. 1268 48

Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF.
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PMID:Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease. 1269 8

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