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)

Hypertension is a major healthcare problem afflicting nearly 50 million individuals in the United States. Despite its strong causal association with cardiovascular disease complications including myocardial infarction, heart failure, and stroke, the majority of patients with hypertension do not achieve optimal blood pressure control. The prevalence of hypertension is expected to increase with the aging population, growing obesity epidemic, and rising incidence of metabolic syndrome. Endothelial dysfunction and reduced nitric oxide (NO) bioactivity represent prominent pathophysiological abnormalities associated with hypertensive cardiovascular disease. Individuals with hypertension exhibit blunted epicardial and resistance vascular dilation to endothelium-derived nitric oxide (EDNO) agonists in the peripheral and coronary circulation that likely contributes to mechanisms of altered vascular tone in hypertension. The amino acid L-arginine serves as the principal substrate for vascular NO production. Numerous studies, though not uniformly, demonstrate a beneficial effect of acute and chronic L-arginine supplementation on EDNO production and endothelial function, and L-arginine has been shown to reduce systemic blood pressure in some forms of experimental hypertension. This brief review discusses the potential role of L-arginine in hypertension, and reviews possible mechanisms of L-arginine action including modulation of EDNO production, alteration of asymmetrical dimethylarginine (ADMA):L-arginine balance, and possible improvement of insulin sensitivity. In view of the rising prevalence of hypertension, randomized human clinical studies investigating the potential therapeutic role of L-arginine may be warranted.
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PMID:L-arginine and hypertension. 1546 90

The endogenous nitric oxide-synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is elevated in patients with increased risk for arteriosclerosis. Obesity is a risk factor for cardiovascular disease. We measured plasma ADMA concentrations in morbidly obese women before and after weight loss following gastroplastic surgery. ADMA and symmetrical dimethyl-L-arginine concentrations were analyzed by HPLC from 34 female patients (age 41 +/- 7 yr) with a body mass index (BMI) of 49 +/- 1 kg/m2 before and 14 months after vertical ring gastroplasty. Age-matched healthy women (BMI < 25 kg/m2; n = 24) were studied as controls. After gastroplastic surgery, BMI decreased to 34 +/- 1 kg/m2 in obese women (P < 0.00001), and ADMA concentrations were reduced from 1.06 +/- 0.06 micromol/liter at baseline to 0.81 +/- 0.04 micromol/liter after weight loss (P < 0.00001). Symmetrical dimethyl-L-arginine plasma levels were not affected. ADMA correlated with high-sensitivity C-reactive protein at baseline (r = 0.42; P < 0.05) and after weight loss (r = 0.56; P < 0.005). No association with blood pressure or plasma lipids could be observed. ADMA concentrations were lower in controls (0.68 +/- 0.04 micromol/liter; P < 0.05) compared with obese patients before or after weight reduction. The decrease of highly elevated ADMA concentrations in morbidly obese patients is paralleled by improvement of parameters associated with the metabolic syndrome after weight loss.
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PMID:Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. 1557 89

Arginine methylation is a post-translational modification resulting in the generation of aDMAs (asymmetrical omega-NG, NG-dimethylated arginines) and sDMAs (symmetrical omega-NG, N'G-dimethylated arginines). The role of arginine methylation in cell signalling and gene expression in T lymphocytes is not understood. In the present study, we report a role for protein arginine methylation in regulating IL-2 (interleukin 2) gene expression in T lymphocytes. Leukaemic Jurkat T-cells treated with a known methylase inhibitor, 5'-methylthioadenosine, had decreased cytokine gene expression, as measured using an NF-AT (nuclear factor of activated T-cells)-responsive promoter linked to the luciferase reporter gene. Since methylase inhibitors block all methylation events, we performed RNA interference with small interfering RNAs against the major PRMT (protein arginine methyltransferases) that generates sDMA (PRMT5). The dose-dependent decrease in PRMT5 expression resulted in the inhibition of both IL-2- and NF-AT-driven promoter activities and IL-2 secretion. By using an sDMA-specific antibody, we observed that sDMA-containing proteins are directly associated with the IL-2 promoter after T-cell activation. Since changes in protein arginine methylation were not observed after T-cell activation in Jurkat and human peripheral blood lymphocytes, our results demonstrate that it is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression.
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PMID:Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5). 1565 70

Vascular dysfunction in chronic renal failure may be linked to reduced nitric oxide (NO) bioactivity and increased circulating concentrations of the endogenous NO synthase inhibitor asymmetrical dimethyl L-arginine (ADMA). The association between ADMA and basal endothelial NO release and endothelium-dependent vasodilation in resistance arteries of chronic renal failure patients is unknown. Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerine, and the endothelium-dependent vasoconstrictor N(G)-monomethyl-L-arginine (L-NMMA) were assessed in 37 peritoneal dialysis patients. L-arginine and ADMA plasma concentrations were measured by HPLC. ADMA (mean +/- SEM: 0.68 +/- 0.02 micromol/L) was associated with basal forearm blood flow (r = -0.33; P < 0.05) and L-NMMA induced vasoconstriction (r = -0.55; P < 0.0005), but not with dilator effects of acetylcholine or nitroglycerine. L-arginine (68 +/- 3 micromol/L) tended to correlate with acetylcholine-induced vasodilation (r = 0.32; P = 0.05) but was not associated with other parameters. ADMA is related to basal but not to acetylcholine-stimulated NO bioactivity in patients on peritoneal dialysis. Impaired endothelium-dependent vasodilation found in chronic renal failure is not explained by elevated circulating NO synthase inhibitors in renal failure.
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PMID:Asymmetrical dimethylarginine plasma concentrations are related to basal nitric oxide release but not endothelium-dependent vasodilation of resistance arteries in peritoneal dialysis patients. 1585 20

The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.
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PMID:Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease. 1594 31

Both eyes of flatfishes are located on one side of the body due to asymmetrical eye migration. The molecular mechanisms underlying such asymmetry is poorly understood. As an initial step, we have adopted suppression subtractive hybridization for the identification of upregulated genes during metamorphosis involving eye migration in Japanese flounder, Paralichthys olicaceus. One of the upregulated genes was identified as the splicing factor arginine/serine rich-3 (SFRS3). Sequence analysis of SFRS3 revealed that it encodes a protein of 168 amino acids containing the typical eukaryotic RNA recognition motif (RRM) and an arginine/serine-rich region. The overall amino acid sequences of the Japanese flounder SFRS3 was highly conserved with that of other organisms. The expression of flounder SFRS3 gene increased sharply from the beginning of metamorphosis and reached a high level of expression at stage H of metamorphosis 43 days after hatching. The SFRS3 gene upregulation was mainly limited to the head region, particularly in the rapidly proliferative tissues, the lateral ethmoid and "skin thickness" on blind side, which are thought as two proliferative tissues to push the eye movement. In spite of the upregulated expression of SFRS3 during metamorphosis, its role in metamorphosis involving eye migration requires further studies.
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PMID:Isolation of SFRS3 gene and its differential expression during metamorphosis involving eye migration of Japanese flounder Paralichthys olivaceus. 1595 Mar 87

AqpZ is a homotetramer of four water-conducting channels that facilitate rapid water movements across the plasma membrane of Escherichia coli. Here we report a 3.2 angstroms crystal structure of the tetrameric AqpZ (tAqpZ). All channel-lining residues in the four monomeric channels are found orientated in nearly identical positions with one marked exception at the narrowest channel constriction, where the side chain of a highly conserved Arg-189 adopts two distinct conformational orientations. In one of the four monomers, the guanidino group of Arg-189 points toward the periplasmic vestibule, opening up the constriction to accommodate the binding of a water molecule through a tridentate H-bond. In the other three monomers, the Arg-189 guanidino group bends over to form an H-bond with carbonyl oxygen of the Thr-183, thus occluding the channel. Therefore, the tAqpZ structure reveals two distinct Arg-189 confirmations associated with water permeation through the channel constrictions. Alternation between the two Arg-189 conformations disrupts continuous flow of water, thus regulating the open probability of the water pore. Further, the difference in Arg-189 displacements is correlated with a strong electron density found between the first transmembrane helices of two open channels, suggesting that the observed Arg-189 conformations are stabilized by asymmetrical subunit interactions in tAqpZ.
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PMID:Crystal structure of AqpZ tetramer reveals two distinct Arg-189 conformations associated with water permeation through the narrowest constriction of the water-conducting channel. 1623 19

The risk of developing cardiovascular disease is greatly increased in patients undergoing renal replacement therapy and, notably, morbidity and mortality due to therapy is much higher in these patients than in the general population. Minimal alterations in renal function, as evidenced by reduced glomerular filtration rate and the presence of albuminuria, have been described as potent cardiovascular risk factors. The classic risk factors only partly explain this difference; hence, we must admit the existence of known and emerging factors associated with increased cardiovascular risk in patients with renal disease. This article provides a review of these factors. It describes the role of hyperphosphoremia and elevated calcium-phosphorous product in the formation of cardiovascular calcifications, the contribution of anemia to left ventricular hypertrophy, and the consequences of accelerated atherogenesis with oxidative stress and a microinflammatory state resulting from endothelial dysfunction. Hyperhomocysteinemia, increased sympathetic nervous system activity, lipoprotein alterations with elevated lipoprotein A, and increases in the concentrations of asymmetrical dimethyl-arginine are other examples of the changes described in this population. Patients with renal disease should be considered to be at high risk for developing cardiovascular disease and candidates for implementation of secondary prevention strategies. It is for this reason that early identification of renal failure, which remains hidden in many cases, is of prime importance.
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PMID:Chronic renal failure: a cardiovascular risk factor. 1633 73

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

The use of drugs for treating neuromuscular impairments that present in the patient admitted to the Intensive Care Unit is virtually inexistent. The use of intravenous immunoglobulins for managing polyneuropathy of the critically ill patient (PCIP) is supported by no evidence. More important is prophylactic therapy, as is the administration of insulin perfusion to prevent hyperglycemia that is associated to increased development of PCIP. New data suggest that the protective mechanism of this perfusion, which normalizes glucose levels, is achieved through the modulation of endothelial dysfunction and lowering levels of asymmetrical di-methyl arginine (ADMA). As for myopathy of the critically ill patient or conditions with prolonged neuromuscular blockade, treatment consists in avoiding the use of several drugs known to be associated with development of these conditions, such as muscle relaxants and aminoglycosides. In relation to acute flaccid paralysis -an infection caused by the Western Nile Virus, anecdotic cases have been reported of improvement with the use steroids or interferon, although routine management remains to be established.
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PMID:[Pharmacological treatment neuromuscular impairments in critically ill patients]. 1676 38


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