The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials.

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Synakiewicz, Anna; Stachowicz-Stencel, Teresa; Adamkiewicz-Drozynska, Elzbieta

2014-11-01

The metabolic differences between normal, healthy cells and neoplastic cells have been exploited by anticancer therapies targeting metabolic pathways. Various studies of malignant processes have demonstrated disturbances in both arginine synthesis and metabolism that enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzyme arginine deiminase (ADI) as a potential antineoplastic therapy. This review summarizes the literature on the potential anti-cancer therapeutics arginine and ADI, an arginine-catabolizing enzyme. The authors searched the MEDLINE database PubMed using the key words: 'arginine, 'ADI', 'arginine in cancer' and 'ADI and cancer'. The authors evaluate prospective randomized studies on cancer patients between 2004 and 2013 as well as ongoing research found through the US National Institutes of Health trial database. The results of current studies are promising but do not give unequivocal answers and so it is impossible to recommend arginine or its enzyme ADI as a therapeutic. In the opinion of the authors, further identification of arginine-dependent malignant tumors and their metabolism should be investigated. Furthermore, the use of these chemicals, in combination with other chemotherapeutics drugs, should be investigated and indeed may improve the success of arginine-depleting enzymes such as pegylated ADI (ADI-PEG20).

Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

KAUST Repository

Shah, Dhawal; Li, Jianguo; Shaikh, Abdul Rajjak; Rajagopalan, Raj

2011-01-01

We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, Γ XP, contrary to conventional thinking that positive Γ XP's indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine's preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine's interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on Γ XP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers (AIChE).

L-Arginine Supplementation and Metabolism in Asthma

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Angela Linderholm

2011-01-01

Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

Arginine Adjunctive Therapy in Active Tuberculosis

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Aliasghar Farazi

2015-01-01

Full Text Available Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18. Results. Arginine supplementation reduced constitutional symptoms (P=0.032 in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P=0.032 and P=0.04 and a reduced CRP at the end of the first month of treatment (P=0.03 versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2.

Arginine affects appetite via nitric oxide in ducks.

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Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

2014-08-01

The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. © Poultry Science Association Inc.

Combinatorial effects of arginine and fluoride on oral bacteria.

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Zheng, X; Cheng, X; Wang, L; Qiu, W; Wang, S; Zhou, Y; Li, M; Li, Y; Cheng, L; Li, J; Zhou, X; Xu, X

2015-02-01

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicating synergy between fluoride and arginine in caries management. Here, we hypothesize that arginine may augment the ecological benefit of fluoride by enriching alkali-generating bacteria in the plaque biofilm and thus synergizes with fluoride in controlling dental caries. Specifically, we assessed the combinatory effects of NaF/arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that arginine synergized with fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of fluoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management. © International & American

Primary assimilation process of triply (/sup 15/N, /sup 14/C and /sup 3/H) labeled arginine in the roots of arginine-fed barley

Energy Technology Data Exchange (ETDEWEB)

Mori, Satoshi [Tokyo Univ. (Japan). Faculty of Agriculture

1981-03-01

To clarify the mechanism of arginine utilization in barley roots, triply labeled (ureido-/sup 15/N, ureido-/sup 14/C and 5-/sup 3/H) arginine was applied to plants precultured with arginine (Arg-plants). (5-/sup 3/H) Arginine was incorporated mainly into ornithine, suggesting that arginase contributes in the first step of arginine metabolism. The arginase activity in the tissues was greatly enhanced by continuous supply of arginine, whereas urease activity was not by the same treatment. The amount of /sup 14/CO/sub 2/ evolved from (ureido-/sup 14/C) arginine in the Arg-plants was several times higher than that in plants treated with NO/sub 3//sup -/(NO/sub 3/-plants), and most /sup 14/C-urea exogenously supplied to detached roots of Arg-plants was immediately decomposed to /sup 14/CO/sub 2/. The urea released from arginine by arginase was cleaved to /sup 15/NH/sub 4//sup +/ + /sup 14/CO/sub 2/ by urease. Most of the /sup 14/CO/sub 2/ was then lost from the root system. On the other hand, the released /sup 15/NH/sub 4//sup +/ was reassimilated into amino acids probably through the pathway of ammonia assimilation. Released (5-/sup 3/H) ornithine was metabolized dominantly to proline.

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

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Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

2017-07-01

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

The effect of arginine on oral biofilm communities.

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Nascimento, M M; Browngardt, C; Xiaohui, X; Klepac-Ceraj, V; Paster, B J; Burne, R A

2014-02-01

Alkali production by oral bacteria via the arginine deiminase system (ADS) increases the pH of oral biofilms and reduces the risk for development of carious lesions. This study tested the hypothesis that increased availability of arginine in the oral environment through an exogenous source enhances the ADS activity levels in saliva and dental plaque. Saliva and supra-gingival plaque samples were collected from 19 caries-free (CF) individuals (DMFT = 0) and 19 caries-active (CA) individuals (DMFT ≥ 2) before and after treatment, which comprised the use of a fluoride-free toothpaste containing 1.5% arginine, or a regular fluoride-containing toothpaste twice daily for 4 weeks. ADS activity was measured by quantification of ammonia produced from arginine by oral samples at baseline, after washout period, 4 weeks of treatment, and 2 weeks post-treatment. Higher ADS activity levels were observed in plaque samples from CF compared to those of CA individuals (P = 0.048) at baseline. The use of the arginine toothpaste significantly increased ADS activity in plaque of CA individuals (P = 0.026). The plaque microbial profiles of CA treated with the arginine toothpaste showed a shift in bacterial composition to a healthier community, more similar to that of CF individuals. Thus, an anti-caries effect may be expected from arginine-containing formulations due in large part to the enhancement of ADS activity levels and potential favorable modification to the composition of the oral microbiome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhibition of protein aggregation: supramolecular assemblies of arginine hold the key.

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Utpal Das

Full Text Available BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Abeta(1-42 peptide is modified. Changes in the hydrodynamic volume of Abeta(1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Abeta(1-42. Arginine increases the solubility of Abeta(1-42 peptide in aqueous medium. It decreases the aggregation of Abeta(1-42 as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation.

Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

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Flynn, K M; Kellihan, H B; Trepanier, L A

2017-08-01

To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the “L-arginine paradox”

International Nuclear Information System (INIS)

Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung

2011-01-01

Highlights: ► Our findings provide a possible solution to the “L-arginine paradox”. ► Extracellular L-arginine concentration is the major determinant of NO production. ► Cellular L-arginine action is limited by cellular ARG transport, not the K m of NOS. ► We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of 15 N 4 -ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, 15 N 4 -ARG, dimethylarginines, and L-citrulline by an LC–MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by 15 N-nitrite or estimated 15 N 3 -citrulline concentrations when 15 N 4 -ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced 15 N 4 -ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by 15 N-nitrite, total nitrite and 15 N 3 -citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside the cell, ARG can no longer gain access to the membrane-bound eNOS. These observations indicate that the “L-arginine paradox” should not consider intracellular ARG

Analysis of an Alanine/Arginine Mixture by Using TLC/FTIR Technique

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Jun Liu

2014-01-01

Full Text Available We applied TLC/FTIR coupled with mapping technique to analyze an alanine/arginine mixture. Narrow band TLC plates prepared by using AgI as a stationary phase were used to separate alanine and arginine. The distribution of alanine and arginine spots was manifested by a 3D chromatogram. Alanine and arginine can be successfully separated by the narrow band TLC plate. In addition, the FTIR spectra of the separated alanine and arginine spots on the narrow band TLC plate are roughly the same as the corresponding reference IR spectra.

Synthesis of the arginine labelled by {sup 15}N on the amidine group; Synthese de l'arginine marquee par {sup 15}N dans le groupe amidine

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Pichat, L; Clement, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

1955-07-01

For some biologic studies, it was necessarily to have (+) arginine marked by nitrogen 15 in the amidine group. This report describes the synthesis of the labelled arginine. The first step is the synthesis of the methyl-isourated hydro-chlorate, the intermediate reactive, from the ClNH{sub 4} isotope. The arginine is obtained from the ornithine which we previously blocked the amino group as cupric complex. The mean yield in arginine reaches 30%, based on the ammonium chloride uses. (M.B.) [French] Pour certaines etudes biologiques, il etait indispensable de disposer de (+) arginine marquee par l'azote 15 dans le groupement amidine. Ce rapport decrit la synthese de l'ariginine marquee. La premiere etape est la synthese du chlorhydrate de methylisouree, intermediaire reactif, a partir du ClNH{sub 4} isotopique. L'obtention de l'arginine est obtenue a partir de l'ornithine dont on a prealablement bloque le groupe amino sous forme de complexe cuivrique. Le rendement global moyen en arginine atteint 30 %, base sur le chlorure d'ammonium utilise. (M.B.)

Modulators of arginine metabolism support cancer immunosurveillance

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Freschi Massimo

2009-01-01

Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

Purification of free arginine from chickpea (Cicer arietinum) seeds.

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Cortés-Giraldo, Isabel; Megías, Cristina; Alaiz, Manuel; Girón-Calle, Julio; Vioque, Javier

2016-02-01

Chickpea is a grain legume widely consumed in the Mediterranean region and other parts of the world. Chickpea seeds are rich in proteins but they also contain a substantial amount of free amino acids, especially arginine. Hence chickpea may represent a useful source of free amino acids for nutritional or pharmaceutical purposes. Arginine is receiving great attention in recent years because it is the substrate for the synthesis of nitric oxide, an important signaling molecule involved in numerous physiological and pathological processes in mammals. In this work we describe a simple procedure for the purification of arginine from chickpea seeds, using nanofiltration technology and an ion-exchange resin, Amberlite IR-120. Arginine was finally purified by precipitation or crystallization, yielding preparations with purities of 91% and 100%, respectively. Chickpea may represent an affordable green source of arginine, and a useful alternative to production by fermentation or protein hydrolysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gliclazide directly inhibits arginine-induced glucagon release

DEFF Research Database (Denmark)

Cejvan, Kenan; Coy, David H; Holst, Jens Juul

2002-01-01

Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

Acellular matrix of bovine pericardium bound with L-arginine

International Nuclear Information System (INIS)

Kim, Hyo Joo; Bae, Jin Woo; Kim, Chun Ho; Lee, Jin Woo; Shin, Jung Woog; Park, Ki Dong

2007-01-01

Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses

Acellular matrix of bovine pericardium bound with L-arginine

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo Joo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Bae, Jin Woo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Kim, Chun Ho [Laboratory of Tissue Engineering, Korea Cancer Center Hospital, Seoul 139-240 (Korea, Republic of); Lee, Jin Woo [Department of Orthopaedic Surgery, College of Medicine, Yonsei University, Seoul 120-749 (Korea, Republic of); Shin, Jung Woog [Department of Biomedical Engineering, Inje University, Gimhae 621-749 (Korea, Republic of); Park, Ki Dong [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

2007-09-15

Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses.

Arginine, citrulline and nitric oxide metabolism in sepsis

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Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

Science.gov (United States)

Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

2005-08-03

To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.

Altered brain arginine metabolism in schizophrenia.

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Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis

DEFF Research Database (Denmark)

Schön, T; Elias, D; Moges, F

2003-01-01

, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor-a. Compared with the human immunodeficiency virus (HIV)-/TB+ placebo group, the HIV-/TB+ patients in the arginine group showed significant improvement......, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV-/TB+ arginine group (100.2 microM (range 90.5-109.9) versus 142.1 microM (range 114.1-170.1)) compared with the HIV-/TB+ placebo group (105.......5 microM (range 93.7-117.3) versus 95.7 microM (range 82.4-108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo. Arginine is beneficial as an adjuvant treatment in human immunodeficiency...

Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

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Shin, Soyoung; Mohan, Srinidi [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Fung, Ho-Leung, E-mail: hlfung@buffalo.edu [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States)

2011-11-04

Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

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Workman, Joanna L; Weber, Michael D; Nelson, Randy J

2011-09-30

Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of methylation on the side-chain pKa value of arginine.

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Evich, Marina; Stroeva, Ekaterina; Zheng, Yujun George; Germann, Markus W

2016-02-01

Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition. © 2015 The Protein Society.

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

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Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

2018-03-01

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p L-arginine than patients with LVSD (p L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

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Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

2016-01-01

to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...

The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis

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Marcus eFulde

2014-08-01

Full Text Available The arginine-ornithine antiporter (ArcD is part of the Arginine Deiminase System (ADS, a catabolic, energy-providing pathway found in a variety of different bacterial species, including the porcine zoonotic pathogen Streptococcus suis. The ADS has recently been shown to play a role in the pathogenicity of S. suis, in particular in its survival in host cells. The contribution of arginine and arginine transport mediated by ArcD, however, has yet to be clarified. In the present study, we showed by experiments using [U-13C6]arginine as a tracer molecule that S. suis is auxotrophic for arginine and that bacterial growth depends on the uptake of extracellular arginine. To further study the role of ArcD in arginine metabolism, we generated an arcD-specific mutant strain and characterized its growth compared to the wild-type (WT strain, a virulent serotype 2 strain. The mutant strain showed a markedly reduced growth rate in chemically defined media supplemented with arginine when compared to the WT strain, indicating that ArcD promotes arginine uptake. To further evaluate the in vivo relevance of ArcD, we studied the intracellular bacterial survival of the arcD mutant strain in an epithelial cell culture infection model. The mutant strain was substantially attenuated, and its reduced intracellular survival rate correlated with a lower ability to neutralize the acidified environment. Based on these results, we propose that ArcD, by its function as an arginine-ornithine antiporter, is important for supplying arginine as substrate of the ADS and, thereby, contributes to biological fitness and virulence of S. suis in the host.

Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

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Staalsø, Jonatan Myrup; Bergström, Anita; Edsen, Troels

2013-01-01

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine...

Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

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El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

2012-04-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

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Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

2016-01-01

We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

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Sunatkari, A. L., E-mail: ashok.sunatkari@rediffmail.com [Department of Physics, Siddhartha College of Arts, Science and Commerce, Fort, Mumbai-400001, India. Email: ashok.sunatkari@rediffmail.com (India); Talwatkar, S. S. [Department of Physics, N.G. Aacharya and D.K. Maratha College of Arts, Science and Commerce, Chembur, Mumbai-400071, India. Email: swarna-81@rediffmail.com (India); Tamgadge, Y. S. [Department of Physics, Mahatma Phule Arts, Commerce & S.R.C. Science College, Warud-444906, India. Email: ystamgadge@gmail.com (India); Muley, G. G., E-mail: gajananggm@yahoo.co.in [Department of Physics, Sant Gadge Baba Amravati University, Amravati-444602 India. Email: gajananggm@yahoo.co.in (India)

2016-05-06

We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

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Vincent Marion

Full Text Available Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl and Villin-Cre mice. Unexpectedly, Ass (fl/fl /VilCre (tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice. Relative to control mice, citrulline production in the splanchnic region of Ass (fl/fl /VilCre (tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass (fl/fl /VilCre (tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2 and transport (Slc25a13, Slc25a15, and Slc3a2, whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver.

Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor

International Nuclear Information System (INIS)

Kimura, Shuhei; Sawatsubashi, Shun; Ito, Saya; Kouzmenko, Alexander; Suzuki, Eriko; Zhao, Yue; Yamagata, Kaoru; Tanabe, Masahiko; Ueda, Takashi; Fujiyama, Sari; Murata, Takuya; Matsukawa, Hiroyuki; Takeyama, Ken-ichi; Yaegashi, Nobuo

2008-01-01

Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressed EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly

Chemical mechanisms of histone lysine and arginine modifications

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Smith, Brian C.; Denu, John M.

2008-01-01

Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, an...

The subcellular compartmentalization of arginine metabolizing enzymes and their role in endothelial dysfunction

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Feng eChen

2013-07-01

Full Text Available The endothelial production of nitric oxide (NO mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle proliferation and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS through the conversion of its substrate, L-arginine to L-citrulline. Reduced access to L-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2 metabolize L-arginine to generate L-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of L-arginine. Indeed, supplemental L-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, L-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis suggesting additional mechanisms. The compartmentalization of intracellular L-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of L-arginine. Indeed the subcellular location of L-arginine metabolizing enzymes plays important functional roles. In endothelial cells, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localtion. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, ASL, co-localize with eNOS and facilitate NO release. This review highlights the importance of the subcellular location of eNOS and arginine transporting and metabolizing enzymes to NO release and cardiovascular disease.

Atropine and ODQ antagonize tetanic fade induced by L-arginine in cats

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J.M. Cruciol-Souza

1999-10-01

Full Text Available Although it has been demonstrated that nitric oxide (NO released from sodium nitrite induces tetanic fade in the cat neuromuscular preparations, the effect of L-arginine on tetanic fade and its origin induced by NO have not been studied in these preparations. Furthermore, atropine reduces tetanic fade induced by several cholinergic and anticholinergic drugs in these preparations, whose mechanism is suggested to be mediated by the interaction of acetylcholine with inhibitory presynaptic muscarinic receptors. The present study was conducted in cats to determine the effects of L-arginine alone or after pretreatment with atropine or 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ on neuromuscular preparations indirectly stimulated at high frequency. Drugs were injected into the middle genicular artery. L-arginine (2 mg/kg and S-nitroso-N-acetylpenicillamine (SNAP; 16 µg/kg induced tetanic fade. The Nw-nitro-L-arginine (L-NOARG; 2 mg/kg alone did not produce any effect, but reduced the tetanic fade induced by L-arginine. D-arginine (2 mg/kg did not induce changes in tetanic fade. The tetanic fade induced by L-arginine or SNAP was reduced by previous injection of atropine (1.0 µg/kg or ODQ (15 µg/kg. ODQ alone did not change tetanic fade. The data suggest that the NO-synthase-GC pathway participates in the L-arginine-induced tetanic fade in cat neuromuscular preparations. The tetanic fade induced by L-arginine probably depends on the action of NO at the presynaptic level. NO may stimulate guanylate cyclase increasing acetylcholine release and thereby stimulating presynaptic muscarinic receptors.

Plasma glucagon responses to L-arginine in various diseases

International Nuclear Information System (INIS)

Morita, Nobuto; Hayakawa, Hiroyuki; Kawai, Kohzo; Noto, Yutaka; Ohno, Taro

1978-01-01

To clarify the mechanism of abnormal glucose metabolism in the secondary diabetes, we examined the dynamics of plasma glucagon levels in various diseases which may accompany glucose intolerance. Plasma glucagon responses to L-arginine were observed in 20 liver cirrhotics, 8 patients with chronic renal failure, 6 patients with chronic pancreatitis, 4 patients, with hyperthyroidism, 22 diabetics and 9 normal controls. Plasma glucagon levels were determined by the radioimmunoassay method of Unger using 125 I-glucagon and antiserum 30K which is specific for pancreatic glucagon. In the cirrhotics, the plasma glucagon responses to L-arginine were significantly higher than in normal controls. The patients whose BSP retention at 45 minutes were above 30% showed higher plasma glucagon responses than in the patients whose BSP retention at 45 minutes were below 30%, suggesting that the more severely the liver was damaged, the more the plasma glucagon levels were elevated. In the patients with chronic renal failure, the plasma glucagon responses to L-arginine were also significantly higher than in normal controls. These abnormal levels were not improved by a hemodialysis, although serum creatinine levels were fairly decreased. In the patients with chronic pancreatitis, the plasma glucagon responses to L-arginine were the same as those in normal controls. In the patients with hyperthyroidism the plasma glucagon responses to L-arginine seemed to be lower than normal controls. In the diabetics, the plasma glucagon responses to L-arginine were almost the same as in normal controls. However their glucagon levels seemed to be relatively high, considering the fact that diabetics had high blood glucose levels. (auth.)

Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

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Sun Yuan

2006-02-01

Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

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Zheng Gong

Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

PRE-EXERCISE ARGININE SUPPLEMENTATION INCREASES TIME TO EXHAUSTION IN ELITE MALE WRESTLERS

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H.U. Yavuz

2014-08-01

Full Text Available Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg-1 body weight or placebo was given to the subjects after 12 hours fasting (during the night for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg-1 · min-1, placebo 52.07±5.21 mL · kg-1 · min-1 or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s compared to placebo (1313±90.8 s (p<0.05. These results suggest that L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects.

The role of the arginine metabolome in pain: implications for sickle cell disease

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Bakshi N

2016-03-01

Full Text Available Nitya Bakshi,1–2 Claudia R Morris3–6 1Division of Pediatric Hematology-Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 2Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 3Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 4Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA; 5Emory-Children’s Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA; 6Pediatric Emergency Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA Abstract: Sickle cell disease (SCD is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO, polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its

L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

Science.gov (United States)

Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

1997-01-21

The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

Radioimmunoassay of [8-D-arginine] deamino-vasopressin (dDAVP)

International Nuclear Information System (INIS)

Slaninova, J.; Barth, T.

1978-01-01

Specific antibodies to [8-D-arginine] deamino-vasopressin (dDAVP) were prepared by immunizing pigs with the conjugate of [8-D-arginine] vasopressin (DVAP) and rabbit immunoglobulin. The specificity of the antibodies was studied by comparing their cross-reactivity with 20 analogues of neurohypophysial hormones. The sensitivity of the developed radioimmunoassay was 30 pg/ml. (authors)

The ArcD1 and ArcD2 arginine/ornithine exchangers encoded in the arginine deiminase (ADI) pathway gene cluster of Lactococcus lactis

NARCIS (Netherlands)

Noens, Elke E E; Kaczmarek, Michał B; Żygo, Monika; Lolkema, Juke S

2015-01-01

The arginine deiminase pathway (ADI) gene cluster in Lactococcus lactis contains two copies of a gene encoding an L-arginine/L-ornithine exchanger, the arcD1 and arcD2 genes. The physiological function of ArcD1 and ArcD2 was studied by deleting the two genes. Deletion of arcD1 resulted in loss of

The do's and don'ts of arginine supplementation | Chetty | South ...

African Journals Online (AJOL)

In the last three decades the nutritional and pharmacologic effects of arginine have been the subject of intense investigation. Taking into consideration the many benefits that have been demonstrated from arginine supplementation, the question remains: “Can we afford not to supplement with this immuno-nutrient”.

L-arginine increases nitric oxide and attenuates pressor and heart ...

African Journals Online (AJOL)

olayemitoyin

heart rate responses to change in posture in sickle cell anemia subjects. 1 .... the standing position and measurements made immediately. Arterial ... pressure was the difference between systolic and diastolic ... Table 3. Effect of L-Arginine Supplementation on Blood Pressure Parameters, Plasma L-Arginine and Nitric Oxide.

Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy.

Directory of Open Access Journals (Sweden)

Michelle Wehling-Henricks

2010-05-01

Full Text Available Duchenne muscular dystrophy (DMD is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial

Effects of dietary L-arginine on orthodontic tooth movement in rats

African Journals Online (AJOL)

Yomi

2012-01-03

Jan 3, 2012 ... arginine in drinking water six days before the insertion of springs to ... Key words: L-Arginine, dietary, orthodontic tooth movement, nitric oxide, root resorption, osteoclast, .... cAMP, interleukin 1-beta and neurotransmitters are.

Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.

Science.gov (United States)

Schmidt, Andreas; Trentini, Débora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

2014-02-01

Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response.

L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

Science.gov (United States)

Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

2018-03-01

The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of

The second case of a young man with L-arginine-induced acute pancreatitis.

Science.gov (United States)

Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

2018-04-21

Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

Preparation of arginine (guanide 14C)

International Nuclear Information System (INIS)

Pichat, L.; Baret, C.

1960-01-01

Reaction of anhydrous ammoniac at 800 deg. C on 14 CO 3 Ba gives rise to barium cyanamide 14 C with a yield of about 98 per cent. Addition on H 2 S on cyanamide 14 C leads to thiourea 14 C with a 85 per cent yield, which is quantitatively transformed into S-ethyl-isothiouronium iodide by treatment with methyl iodide. This 14 C-isothiouronium salt is used to introduce 14 C guanide group in α-N-tosyl-ornithine; tosyl group in α-N-tosyl-arginine thus obtained is then removed by hydrolysis with hydrochloric acid. Arginine is separated as flavianic acid salt and is purified on exchange resin Dowex-50. The overall yield based on 14 CO 3 Ba is 25 per cent. (author) [fr

Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

International Nuclear Information System (INIS)

Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

2005-01-01

The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca 2+ transients and cellular uptake of L-[ 3 H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[ 3 H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine

Short Arginine Motifs Drive Protein Stickiness in the Escherichia coli Cytoplasm.

Science.gov (United States)

Kyne, Ciara; Crowley, Peter B

2017-09-19

Although essential to numerous biotech applications, knowledge of molecular recognition by arginine-rich motifs in live cells remains limited. 1 H, 15 N HSQC and 19 F NMR spectroscopies were used to investigate the effects of C-terminal -GR n (n = 1-5) motifs on GB1 interactions in Escherichia coli cells and cell extracts. While the "biologically inert" GB1 yields high-quality in-cell spectra, the -GR n fusions with n = 4 or 5 were undetectable. This result suggests that a tetra-arginine motif is sufficient to drive interactions between a test protein and macromolecules in the E. coli cytoplasm. The inclusion of a 12 residue flexible linker between GB1 and the -GR 5 motif did not improve detection of the "inert" domain. In contrast, all of the constructs were detectable in cell lysates and extracts, suggesting that the arginine-mediated complexes were weak. Together these data reveal the significance of weak interactions between short arginine-rich motifs and the E. coli cytoplasm and demonstrate the potential of such motifs to modify protein interactions in living cells. These interactions must be considered in the design of (in vivo) nanoscale assemblies that rely on arginine-rich sequences.

Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death.

Science.gov (United States)

Movafegh, Bahareh; Jalal, Razieh; Mohammadi, Zobeideh; Aldaghi, Seyyede Araste

2018-04-11

Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin (0.5 μM) and poly-L-arginine (1 μg ml-1) caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Accumulation of Citrulline by Microbial Arginine Metabolism during Alcoholic Fermentation of Soy Sauce.

Science.gov (United States)

Fang, Fang; Zhang, Jiran; Zhou, Jingwen; Zhou, Zhaohui; Li, Tieqiao; Lu, Liling; Zeng, Weizhu; Du, Guocheng; Chen, Jian

2018-03-07

Citrulline, the major precursor of ethyl carbamate in soy sauce, is an intermediate catabolite of arginine produced by bacteria present in soy sauce moromi mash. Pediococcus acidilactici is responsible for the formation of citrulline during the lactic acid fermentation process of soy sauce. However, citrulline accumulation during the alcoholic fermentation process and the corresponding bacteria involved have not been identified. Salt-tolerant, arginine-utilizing bacteria were isolated from moromi mash during the alcoholic fermentation process. Under normal cultivation conditions, arginine utilization by these strains did not contribute to citrulline accumulation. However, the conversion of arginine to citrulline by these bacteria increased when cultivated during the alcoholic fermentation process. Additionally, the ethanol-enhanced solubility of free fatty acids in moromi mash stimulated the accumulation of citrulline. Staphylococcus exhibited the highest capability in the conversion of arginine to citrulline.

L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

Science.gov (United States)

Mansoor, Jim K; Morrissey, Brian M; Walby, William F; Yoneda, Ken Y; Juarez, Maya; Kajekar, Radhika; Severinghaus, John W; Eldridge, Marlowe W; Schelegle, Edward S

2005-01-01

We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

Sided functions of an arginine-agmatine antiporter oriented in liposomes.

Science.gov (United States)

Tsai, Ming-Feng; Fang, Yiling; Miller, Christopher

2012-02-28

The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C-AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress.

Effect of iron, taurine and arginine on rat hepatic fibrosis

International Nuclear Information System (INIS)

Song Liangwen; Wang Dewen; Cui Xuemei

1997-01-01

Objective: The promotion role of iron on pathogenesis of hepatic fibrosis and the protective role of taurine and L-arginine against hepatic fibrosis were studied. Method: The model of rat radiation hepatic fibrosis was used. Experimental rats were divided into 0 Gy, 30 Gy, 30 Gy + iron, 30 Gy + taurine and 30 Gy + L-arginine groups. Serum iron, liver tissue hydroxyproline (Hyp) and malondialdehyde (MDA) were measured one and three months respectively after irradiation of hepatic tissue, production and distribution characteristics of hepatic tissue type I and III collagen were observed with a polarizing microscope. Results: Administration of iron agent could significantly increase hepatic tissue MDA content and serum iron concentration, one month after irradiation, hepatic tissue Hyp in 30 Gy + iron group began to increase, and collagen in hepatic tissue obviously increased. Taurine and L-arginine could reduce serum iron concentration and decrease production of hepatic fissure Hyp. Conclusion: Exogenous iron agent could promote early development of radiation hepatic fibrosis; taurine and arginine could diminish pathologic alteration of hepatic fibrosis to a certain extent

Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.

Science.gov (United States)

Moreno, Jorge; Echeverria, Julian; Silva, Andrea; Escudero, Andrea; Petzold, Guillermo; Mella, Karla; Escudero, Carlos

2017-07-01

Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50  ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.

Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

Science.gov (United States)

Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

2018-04-12

Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

Activities of arginine and ornithine decarboxylases in various plant species.

Science.gov (United States)

Birecka, H; Bitonti, A J; McCann, P P

1985-10-01

In extracts from the youngest leaves of Avena sativa, Hordeum vulgare, Zea Mays, Pisum sativum, Phaseolus vulgaris, Lactuca sativa, and four pyrrolizidine alkaloid-bearing species of Heliotropium, the activities of ornithine decarboxylase, close to V(max), ranged between traces and 1.5 nanomoles per hour per gram fresh weight when based on putrescine formed during incubation with labeled ornithine. The arginine decarboxylase activities in the same extracts ranged between 8 and 8000 nanomoles per hour per gram fresh weight being lowest in the borages and highest in oat and barley. alpha-Difluoromethylornithine and alpha-difluoromethylarginine inhibited ornithine and arginine decarboxylases, respectively, in all species. Agmatine, putrescine, spermidine, and spermine were found in all, diaminopropane in eight, and cadaverine in three species.No correlation was observed between arginine or ornithine decarboxylase level and the levels of total polyamines. The in vitro decarboxylase activities found in the borages cannot explain the high accumulation of putrescine-derived pyrrolizidines in their youngest leaves if the pyrrolizidines are produced in situ from arginine and/or ornithine as precursors; other possibilities are discussed.In assays of ornithine decarboxylase, an interference of decarboxylation not due to this enzyme was observed in extracts from all species. In arginine decarboxylase assays, the interfering decarboxylation as well as the interference of arginase were apparent in two species. Addition of aminoguanidine was needed to suppress oxidative degradation of putrescine and agmatine during incubation of extracts from pea, bean, lettuce, Heliotropium angiospermum, and Heliotropium indicum.

EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

Science.gov (United States)

Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

2016-01-01

L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

Energy Technology Data Exchange (ETDEWEB)

Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Kang, Misun [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Rho, Jaerang, E-mail: jrrho@cnu.ac.kr [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); GRAST, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of)

2010-01-01

Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

Action of arginine for protection of ulcerative colitis by dextran sodium sulphate (DSS)

International Nuclear Information System (INIS)

Andrade, Maria Emilia Rabelo

2016-01-01

Recent studies have demonstrated the benefits of immunomodulators, such as arginine, in the regulation of inflammatory responses and trophism of the intestinal mucosa. The aim of this study was to evaluate the possible mechanisms action of arginine (pretreatment or treatment) in experimental model of ulcerative colitis induced by dextran sodium sulfate (DSS). C57BL/6 mice were randomized into 5 groups: Control group (C): standard diet and water; Arginine group (ARG): diet supplementation with arginine and water; Colitis group (COL): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. After this, all the mice were euthanized and blood, organs and intestinal fluid were collected for carrying out analyzes. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological analysis (histological score, morphometric analysis, collagen and mucins stain), nitrate and nitrite, cytokines and chemokines, secretory immunoglobulin A (sIgA), inflammatory infiltrate and oxidative stress were performed. The ARG group did not show difference compared to group C in the investigated parameters (C vs ARG: p> 0.05). The COL group showed increased IP (C vs COL: p < 0.05) and BT (C vs COL: p <0.05). In the histological analysis, the COL group showed severe inflammation and reduction the crypts length. In addition, in the group COL observed increase infiltration of eosinophils, neutrophils and macrophages in the colon, increase cytokine IL-17 and chemokine KC in serum and oxidative stress in the colon (COL vs C: p <0.05). In the arginine-supplemented groups (PT and T) was observed decrease IP and BT to blood, liver and lung (PT and T vs Col: p <0.05). Histological analysis showed that the arginine (PT and T) preserved the intestinal mucosa and crypts

Effects of arginine and phytogenic additive supplementation on performance and health of brown-egg layers

Directory of Open Access Journals (Sweden)

Vitor Barbosa Fascina

Full Text Available ABSTRACT This study was performed to evaluate the effects of the association of different digestible arginine and phytogenic additive dietary levels on performance and health status of brown-egg layers. In this study, a total of 504 33-week-old Hisex Brown layers were distributed into a completely randomized experimental design to a 4 × 3 factorial arrangement (dietary digestible arginine levels: 880, 968, 1056, or 1144 mg/kg of feed × phytogenic additive levels: 0, 100, and 200 mg/kg of feed with six replicate cages of seven birds per cage. The phytogenic additive was composed of extracts of Baccharis dracunculifolia (40%, Astragalus membranaceus lipopolysaccharides (20%, cinnamon, and grape seed (20%. Feed intake was reduced when diets containing 1056 mg of arginine were supplemented with 100 or 200 mg phytogenic additive per kg. Feed conversion ratio was improved when diets were supplemented with 100 mg of phytogenic additive or with 1056 mg of arginine per kg of feed. Egg mass was increased when diets were supplemented with 1056 mg arginine per kg of feed. Arginine supplementation quadratically increased albumen percentage and reduced yolk percentage. Higher arginine and phytogenic additive levels reduced heterophyl:lymphocyte ratio and blood uric acid, total cholesterol, very-low density lipoprotein, and triglyceride levels. Dietary supplementation of 100 mg of phytogenic additive associated with high arginine levels increased nitric oxide production by peritoneal macrophages and 1056 mg of arginine increased antibodies titers against Newcastle disease virus. Blood and intestinal malonaldehyde levels were reduced when 200 mg of the phytogenic additive was added. Dietary supplementation of 968 mg of arginine or 100 mg of a phytogenic additive (40% Baccharis dracunculifolia, 20% Astragalus membranaceus, 20% cinnamon, and 20% grape seed extracts per kilogram of diet improves the feed conversion ratio and associated inclusion of 1144 mg of

Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

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Chongyuan Wang

Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

Multiple Arginine Residues Are Methylated in Drosophila Mre11 and Required for Survival Following Ionizing Radiation.

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Yuan, Qing; Tian, Ran; Zhao, Haiying; Li, Lijuan; Bi, Xiaolin

2018-05-31

Mre11 is a key player for DNA double strand break repair. Previous studies have shown that mammalian Mre11 is methylated at multiple arginines in its C-terminal Glycine-Arginine-Rich motif (GAR) by protein arginine methyltransferase PRMT1. Here, we found that the Drosophila Mre11 is methylated at arginines 559, 563, 565, and 569 in the GAR motif by DART1, the Drosophila homolog of PRMT1. Mre11 interacts with DART1 in S2 cells, and this interaction does not require the GAR motif. Arginines methylated Mre11 localizes exclusively in the nucleus as soluble nuclear protein or chromatin-binding protein. To study the in vivo functions of methylation, we generated the single Arg-Ala and all Arginines mutated flies. We found these mutants were sensitive to ionizing radiation. Furthermore, Arg-Ala mutated flies had no irradiation induced G2/M checkpoint defect in wing disc and eye disc. Thus, we provided evidence that arginines in Drosophila Mre11 are methylated by DART1 methytransferase and flies loss of arginine methylation are sensitive to irradiation. Copyright © 2018 Yuan et al.

Weissella halotolerans W22 combines arginine deiminase and ornithine decarboxylation pathways and converts arginine to putrescine

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Pereira, C. I.; San Romao, M. V.; Lolkema, J. S.; Barreto Crespo, M. T.; Baretto Crespo, M.

2009-01-01

Aims: To demonstrate that the meat food strain Weissella halotolerans combines an ornithine decarboxylation pathway and an arginine deiminase (ADI) pathway and is able to produce putrescine, a biogenic amine. Evidence is shown that these two pathways produce a proton motive force (PMF). Methods and

Expression pattern of a nuclear encoded mitochondrial arginine-ornithine translocator gene from Arabidopsis

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Schneider Anja

2003-01-01

Full Text Available Abstract Background Arginine and citrulline serve as nitrogen storage forms, but are also involved in biosynthetic and catabolic pathways. Metabolism of arginine, citrulline and ornithine is distributed between mitochondria and cytosol. For the shuttle of intermediates between cytosol and mitochondria transporters present on the inner mitochondrial membrane are required. Yeast contains a mitochondrial translocator for ornithine and arginine, Ort1p/Arg11p. Ort1p/Arg11p is a member of the mitochondrial carrier family (MCF essential for ornithine export from mitochondria. The yeast arg11 mutant, which is deficient in Ort1p/Arg11p grows poorly on media lacking arginine. Results High-level expression of a nuclear encoded Arabidopsis thaliana homolog (AtmBAC2 of Ort1p/Arg11p was able to suppress the growth deficiency of arg11. RT-PCR analysis demonstrated expression of AtmBAC2 in all tissues with highest levels in flowers. Promoter-GUS fusions showed preferential expression in flowers, i.e. pollen, in the vasculature of siliques and in aborted seeds. Variable expression was observed in leaf vasculature. Induction of the promoter was not observed during the first two weeks in seedlings grown on media containing NH4NO3, arginine or ornithine as sole nitrogen sources. Conclusion AtmBAC2 was isolated as a mitochondrial transporter for arginine in Arabidopsis. The absence of expression in developing seeds and in cotyledons of seedlings indicates that other transporters are responsible for storage and mobilization of arginine in seeds.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

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Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2018-05-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

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Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

2017-12-01

The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation of host cells.

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Awasthi, Vikky; Chauhan, Rubika; Chattopadhyay, Debprasad; Das, Jyoti

2017-01-01

Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

Arginine intake and risk of coronary heart disease mortality in elderly men

NARCIS (Netherlands)

Oomen, C.M.; Erk, van M.J.; Feskens, E.J.M.; Kok, F.J.; Kromhout, D.

2000-01-01

From experimental studies, the hypothesis is derived that the amino acid arginine, the precursor of NO, could restore the impaired endothelial function and increased platelet activation observed in atherosclerosis. We investigated whether dietary intake of arginine is associated with reduced

The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome☆

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El-Hattab, Ayman W.; Emrick, Lisa T.; Williamson, Kaitlin C.; Craigen, William J.; Scaglia, Fernando

2013-01-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials. PMID:25411654

The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome.

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El-Hattab, Ayman W; Emrick, Lisa T; Williamson, Kaitlin C; Craigen, William J; Scaglia, Fernando

2013-12-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.

Efficacy L-Arginine In Patients With Nonalcoholic Steatohepatitis Associated With Metabolic Syndrome

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Oleksandr Fediv

2015-01-01

Full Text Available Abstract Background and Purpose Recent research in the field of hematology indicate that among the many pathogenic mechanisms of development and progression of nonalcoholic steatohepatitis NASH which occurs on the background of the metabolic syndrome an important role is played by endothelial dysfunction and violations of haemocoagulation. The aim of this research was to study the effectiveness of L-arginine as it corrects endothelial dysfunction and disorders of homeostasis haemocoagulation link in patients with NASH associated with the metabolic syndrome. Subjects and Methods 128 patients with nonalcoholic steatohepatitis associated with metabolic syndrome were examined. Some patients 63 persons received standard treatment according to national guidelines. To another group 65 patients on the background of basic therapy L-arginine hydrochloride followed by transition to oral form of L-arginine aspartate was administered. Blood levels of stable nitrogen monoxide metabolites nitrites nitrates endothelin-1 and plasma recalcification time prothrombin time thrombin time activated partial thromboplastin time fibrinogen plasma level activity of antithrombin III and coagulation factor XIII potential activity of plasminogen plasma fibrinolytic blood activity were studied. Results Originally significantly increased levels of endothelin-1 decreased after the therapy in all studied groups but more noticeable changes in the group with L-arginine appointment were observed p0.05. In the studied groups normalization of stable nitrogen monoxide metabolites after treatment was also noticed. Significant p0.05 increase in all haemocoagulation time characteristics and activities of antithrombin-III and factor XIII was found. The positive effect of L-arginine on blood fibrinolytic activity was noted. Discussion and Conclusion Combined therapy of nonalcoholic steatohepatitis associated with metabolic syndrome with a differentiated degreeal L-arginine assignment by

Kidney Mass Reduction Leads to l-Arginine Metabolism-Dependent Blood Pressure Increase in Mice.

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Pillai, Samyuktha Muralidharan; Seebeck, Petra; Fingerhut, Ralph; Huang, Ji; Ming, Xiu-Fen; Yang, Zhihong; Verrey, François

2018-02-25

Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2 -/- ) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure. UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Functional and neurochemical profile of place learning after L-nitro-arginine in the rat

DEFF Research Database (Denmark)

Mogensen, Jesper; Wörtwein, Gitta; Hasman, Andreas

1995-01-01

Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning......Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning...

Potentiality of application of the conductometric L-arginine biosensors for the real sample analysis

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Jaffrezic-Renault N.

2012-12-01

Full Text Available Aim. To determine an influence of serum components on the L-arginine biosensor sensitivity and to formulate practical recommendations for its reliable analysis. Methods. The L-arginine biosensor comprised arginase and urease co-immobilized by cross-linking. Results. The biosensor specificity was investigated based on a series of representative studies (namely, through urea determination in the serum; inhibitory effect studies of mercury ions; high temperature treatment of sensors; studying the biosensor sensitivity to the serum treated by enzymes, and selectivity studies. It was found that the response of the biosensor to the serum injections was determined by high sensitivity of the L-arginine biosensor toward not only to L-arginine but also toward two other basic amino acids (L-lysine and L-histidine. Conclusions. A detailed procedure of optimization of the conductometric biosensor for L-arginine determination in blood serum has been proposed.

Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

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Musalmah Mazlan

2017-01-01

Full Text Available Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.

Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

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Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

2013-01-01

Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

In vivo whole body and organ arginine metabolism during endotoxemia (sepsis) is dependent on mouse strain and gender

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Luiking, Y. C.; Hallemeesch, M. M.; Vissers, Y. L. J.; Lamers, W. H.; Deutz, N. E. P.

2004-01-01

Arginine metabolism involves various organs such as the kidney, the intestines, and the liver, which act together in an interorgan axis. Major pathways for arginine production are protein breakdown and de novo arginine production from citrulline; disposal of arginine is mainly used for protein

Theoretical study about L-arginine complexes formation with thiotriazolin

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L. I. Kucherenko

2017-02-01

Full Text Available Brain vascular diseases are one of the leading causes of morbidity, mortality and disability of population in the industrialized countries of the world. An important element of this problem’s solution is the creation of new highly effective and safe drugs, which would lead to mortality reduction, to increase in life expectancy and quality of life. Therefore it is interesting to create a new combined drug based on L-arginine and thiotriazolin. Purpose of the study: to consider the possible structure and energy characteristics of complexes formed by L-arginine, 3-methyl-1,2,4-triazolyl-5-thioacetate (MTTA and morpholine. Calculation method. The initial approximation to the complex geometry was obtained using molecular docking with the help of AutoDock Vina program. The obtained ternary complexes were pre-optimized by semi-empirical PM7 method with modeling the impact of the environment by COSMO method. The calculations were carried out using MOPAC2012 program. Then they were optimized by B97-D3/SVP + COSMO (Water dispersion-corrected DFT-D with geometrical spreading correction on insufficiency of gCP basis set. A more accurate calculation of the solvation energy was conducted by SMD. The calculations by density functional method were carried out using the ORCA 3.0.3 software. Energy complex formation in solution was calculated as the difference of the Gibbs free energy of the solvated complex and its individual components. Results. Quantum chemical calculations show, that thiotriazolin and L-arginine are able to form ternary complexes, where molecules are linked by multiple hydrogen bonds. The calculation data suggest, that studied complexes are thermodynamically unstable in solution. The energies of them are positive, but rather low despite charge gain of a number of intermolecular hydrogen bonds. Finding. Based on the results of the conducted quantum-chemical study of a three components system (MTTA, morpholine, and L-arginine it is possible

Activities of Arginine and Ornithine Decarboxylases in Various Plant Species 1

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Birecka, Helena; Bitonti, Alan J.; McCann, Peter P.

1985-01-01

In extracts from the youngest leaves of Avena sativa, Hordeum vulgare, Zea Mays, Pisum sativum, Phaseolus vulgaris, Lactuca sativa, and four pyrrolizidine alkaloid-bearing species of Heliotropium, the activities of ornithine decarboxylase, close to Vmax, ranged between traces and 1.5 nanomoles per hour per gram fresh weight when based on putrescine formed during incubation with labeled ornithine. The arginine decarboxylase activities in the same extracts ranged between 8 and 8000 nanomoles per hour per gram fresh weight being lowest in the borages and highest in oat and barley. α-Difluoromethylornithine and α-difluoromethylarginine inhibited ornithine and arginine decarboxylases, respectively, in all species. Agmatine, putrescine, spermidine, and spermine were found in all, diaminopropane in eight, and cadaverine in three species. No correlation was observed between arginine or ornithine decarboxylase level and the levels of total polyamines. The in vitro decarboxylase activities found in the borages cannot explain the high accumulation of putrescine-derived pyrrolizidines in their youngest leaves if the pyrrolizidines are produced in situ from arginine and/or ornithine as precursors; other possibilities are discussed. In assays of ornithine decarboxylase, an interference of decarboxylation not due to this enzyme was observed in extracts from all species. In arginine decarboxylase assays, the interfering decarboxylation as well as the interference of arginase were apparent in two species. Addition of aminoguanidine was needed to suppress oxidative degradation of putrescine and agmatine during incubation of extracts from pea, bean, lettuce, Heliotropium angiospermum, and Heliotropium indicum. PMID:16664442

Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test

OpenAIRE

Tschuor, F

2011-01-01

Background: Responsiveness of β-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. Hypothesis: Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. Animals: 17 cats with diabetes, 7 healthy cats. Methods: Response to IVAST was assessed by calculating insulin and glucagon area under the c...

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

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Ruijter Jan M

2008-11-01

Full Text Available Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS, ornithine aminotransferase (OAT, argininosuccinate synthetase (ASS, arginase-1 (ARG1, arginase-2 (ARG2, and nitric-oxide synthase (NOS were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

Tuning interionic interaction by rationally controlling solution pH for highly selective colorimetric sensing of arginine.

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Qian, Qin; Hao, Jie; Ma, Wenjie; Yu, Ping; Mao, Lanqun

2016-04-01

Direct selective sensing of arginine in central nervous systems remains very essential to understanding of the molecular basis of some physiological events. This study presents the first demonstration on a simple yet effective method for arginine sensing with gold nanoparticles (Au-NPs) as the signal readout. The rationale for the method is based on the pH-dependent feature of the interionic interaction between cysteine and arginine. At pH 6.0, cysteine can only interact with arginine through the ion-pair interaction and such interaction can lead to the changes in both the solution color and UV-vis spectrum of the cysteine-protected Au-NPs upon the addition of arginine. These changes are further developed into an analytical strategy for effective sensing of arginine by rationally controlling the pH values of Au-NP dispersions with the ratio of the absorbance at 650 nm (A 650) to that at 520 nm (A 520) (A 650/A 520) as a parameter for analysis. The method is responsive to arginine without the interference from other species in the cerebral system; under the optimized conditions, the A 650/A 520 values are linear with the concentration of arginine within a concentration range from 0.80 to 64 μM, yet remain unchanged with the addition of other kinds of amino acids or the species in the central nervous system into the Au-NPs dispersion containing cysteine. The method demonstrated here is reliable and robust and could thus be used for detection of the increase of arginine in central nervous systems.

Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods

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Cabrera-Luque Juan

2008-09-01

Full Text Available Abstract Background The efficient conversion of ammonia, a potent neurotoxin, into non-toxic metabolites was an essential adaptation that allowed animals to move from the aquatic to terrestrial biosphere. The urea cycle converts ammonia into urea in mammals, amphibians, turtles, snails, worms and many aquatic animals and requires N-acetylglutamate (NAG, an essential allosteric activator of carbamylphosphate synthetase I (CPSI in mammals and amphibians, and carbamylphosphate synthetase III (CPSIII in fish and invertebrates. NAG-dependent CPSI and CPSIII catalyze the formation of carbamylphosphate in the first and rate limiting step of ureagenesis. NAG is produced enzymatically by N-acetylglutamate synthase (NAGS, which is also found in bacteria and plants as the first enzyme of arginine biosynthesis. Arginine is an allosteric inhibitor of microbial and plant NAGS, and allosteric activator of mammalian NAGS. Results Information from mutagenesis studies of E. coli and P. aeruginosa NAGS was combined with structural information from the related bacterial N-acetylglutamate kinases to identify four residues in mammalian NAGS that interact with arginine. Substitutions of these four residues were engineered in mouse NAGS and into the vertebrate-like N-acetylglutamate synthase-kinase (NAGS-K of Xanthomonas campestris, which is inhibited by arginine. All mutations resulted in arginine losing the ability to activate mouse NAGS, and inhibit X. campestris NAGS-K. To examine at what point in evolution inversion of arginine effect on NAGS occur, we cloned NAGS from fish and frogs and examined the arginine response of their corresponding proteins. Fish NAGS were partially inhibited by arginine and frog NAGS were activated by arginine. Conclusion Difference in arginine effect on bacterial and mammalian NAGS most likely stems from the difference in the type of conformational change triggered by arginine binding to these proteins. The change from arginine

The impact of arginine-modified chitosan-DNA nanoparticles on the function of macrophages

Energy Technology Data Exchange (ETDEWEB)

Liu Lanxia; Bai Yuanyuan; Song Chunni; Zhu Dunwan; Song Liping; Zhang Hailing; Dong Xia; Leng Xigang, E-mail: lengxg@bme.org.c [Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Laboratory of Bioengineering (China)

2010-06-15

It has been demonstrated that incorporation of arginine moieties into chitosan significantly elevates the transgenic efficacy of the chitosan. However, little is known about the impact of arginine-modified chitosan on the function of macrophages, which play a vitally important role in the inflammatory response of the body to foreign substances, especially particulate substances. This study was designed to investigate the impact of arginine-modified chitosan/DNA nanoparticles on the function of the murine macrophage through observation of phagocytic activity and production of pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-10, IL-12, and TNF-{alpha}). Results showed that both chitosan/DNA nanoparticles and arginine-modified chitosan/DNA nanoparticles, containing 20 {mu}g/mL DNA, were internalized by almost all the macrophages in contact. This led to no significant changes, compared to the non-exposure group, in production of cytokines and phagocytic activity of the macrophages 24 h post co-incubation, whereas exposure to LPS induced obviously elevated cytokine production and phagocytic activity, suggesting that incorporation of arginine moieties into chitosan does not have a negative impact on the function of the macrophages.

A role for PPARα in the regulation of arginine metabolism and nitric oxide synthesis.

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Guelzim, Najoua; Mariotti, François; Martin, Pascal G P; Lasserre, Frédéric; Pineau, Thierry; Hermier, Dominique

2011-10-01

The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets containing either saturated fatty acids (COCO diet) or 18:3 n-3 (LIN diet). Metabolic markers of arginine metabolism were assayed in urine and plasma. mRNA levels of arginases and NOS were determined in liver. Whole-body NO synthesis and the conversion of systemic arginine into urea were assessed by using (15)N(2)-guanido-arginine and measuring urinary (15)NO(3) and [(15)N]-urea. PPARα deficiency resulted in a markedly lower whole-body NO synthesis, whereas the conversion of systemic arginine into urea remained unaffected. PPARα deficiency also increased plasma arginine and decreased citrulline concentration in plasma. These changes could not be ascribed to a direct effect on hepatic target genes, since NOS mRNA levels were unaffected, and arginase mRNA levels decreased in KO mice. Despite the low level in the diet, the nature of the fatty acids modulated some effects of PPARα deficiency, including plasma arginine and urea, which increased more in KO mice fed the LIN diet than in those fed the COCO diet. In conclusion, PPARα is largely involved in normal whole-body NO synthesis. This warrants further study on the potential of PPARα activation to maintain NO synthesis in the initiation of the metabolic syndrome.

Indian women of childbearing age do not metabolically conserve arginine as do American and Jamaican women.

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Kao, Christina C; Hsu, Jean W; Dwarkanath, Pratibha; Karnes, Jeffrey M; Baker, Tameka M; Bohren, Kurt M; Badaloo, Asha; Thame, Minerva M; Kurpad, Anura V; Jahoor, Farook

2015-05-01

In a previous study in pregnant American women, we reported that arginine flux and nitric oxide synthesis increased in trimester 2. More recently, we reported that Indian women do not increase arginine flux during pregnancy as their American or Jamaican counterparts do. The purpose of this study was to determine whether Indian women of childbearing age are producing less arginine and/or catabolizing more arginine and therefore have less available for anabolic pathways than do Jamaican and American women. Thirty healthy women aged 28.3 ± 0.8 y from the United States, India, and Jamaica (n = 10/group) were given 6 h primed, constant intravenous infusions of guanidino-¹⁵N₂-arginine, 5,5-²H₂-citrulline, ¹⁵N₂-ornithine, and ring-²H₅-phenylalanine, in addition to primed, oral doses of U-¹³C₆-arginine in both the fasting and postprandial states. An oral dose of deuterium oxide was also given to determine fat-free mass (FFM). Compared with American women, Indian and Jamaican women had greater ornithine fluxes (μmol · kg fat FFM⁻¹ · h⁻¹) in the fasting and postprandial states (27.3 ± 2.5 vs. 39.6 ± 3.7 and 37.2 ± 2.0, respectively, P = 0.01), indicating greater arginine catabolism. However, Jamaican women had a higher endogenous arginine flux than did Indian and American women in the fasting (66.1 ± 3.1 vs. 54.2 ± 3.1 and 56.1 ± 2.1, respectively, P = 0.01) and postprandial (53.8 ± 2.2 vs. 43.7 ± 4.9 and 42.8 ± 3.1, respectively, P = 0.06) states. As a consequence, Indian women had lower arginine bioavailability (μmol · kg FFM⁻¹ · h⁻¹) in the fasting state (42.0 ± 2.6) than did American (49.9 ± 1.3, P = 0.045) and Jamaican (55.5 ± 3.5, P = 0.004) women, as well as in the postprandial state (40.7 ± 3.5 vs. 51.8 ± 1.2 and 57.5 ± 3.2, respectively, P = 0.001). Compared with American and Jamaican women, Indian women of childbearing age have a decreased arginine supply because of increased arginine catabolism without an

Characterization of arginine decarboxylase from Dianthus caryophyllus.

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Ha, Byung Hak; Cho, Ki Joon; Choi, Yu Jin; Park, Ky Young; Kim, Kyung Hyun

2004-04-01

Arginine decarboxylase (ADC, EC 4.1.1.9) is a key enzyme in the biosynthesis of polyamines in higher plants, whereas ornithine decarboxylase represents the sole pathway of polyamine biosynthesis in animals. Previously, we characterized a genomic clone from Dianthus caryophyllus, in which the deduced polypeptide of ADC was 725 amino acids with a molecular mass of 78 kDa. In the present study, the ADC gene was subcloned into the pGEX4T1 expression vector in combination with glutathione S-transferase (GST). The fusion protein GST-ADC was water-soluble and thus was purified by sequential GSTrap-arginine affinity chromatography. A thrombin-mediated on-column cleavage reaction was employed to release free ADC from GST. Hiload superdex gel filtration FPLC was then used to obtain a highly purified ADC. The identity of the ADC was confirmed by immunoblot analysis, and its specific activity with respect to (14)C-arginine decarboxylation reaction was determined to be 0.9 CO(2) pkat mg(-1) protein. K(m) and V(max) of the reaction between ADC and the substrate were 0.077 +/- 0.001 mM and 6.0 +/- 0.6 pkat mg(-1) protein, respectively. ADC activity was reduced by 70% in the presence of 0.1 mM Cu(2+) or CO(2+), but was only marginally affected by Mg(2+), or Ca(2+) at the same concentration. Moreover, spermine at 1 mM significantly reduced its activity by 30%.

tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori.

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Cerda, Oscar A; Núñez-Villena, Felipe; Soto, Sarita E; Ugalde, José Manuel; López-Solís, Remigio; Toledo, Héctor

2011-01-01

About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat) was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR) by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

tlpA gene expression is required for arginine and bicarbonate chemotaxis in Helicobacter pylori

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Oscar A Cerda

2011-01-01

Full Text Available About half of the human population is infected with Helicobacter pylori, a bacterium causing gastritis, peptic ulcer and progression to gastric cancer. Chemotaxis and flagellar motility are required for colonization and persistence of H. pylori in the gastric mucus layer. It is not completely clear which chemical gradients are used by H. pylori to maintain its position. TlpA, a chemotaxis receptor for arginine/ bicarbonate, has been identified. This study aimed to find out whether tlpA gene expression is required for the chemotactic response to arginine/bicarbonate. Wild-type motile H. pylori ATCC 700392 and H. pylori ATCC 43504, a strain having an interrupted tlpA gene, were used. Also, a tlpA-knockout mutant of H. pylori 700392 (H. pylori 700-tlpA::cat was produced by homologous recombination. Expression of tlpA was assessed by a Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR assay. Chemotaxis was measured as a Relative Chemotaxis Response (RCR by a modified capillary assay. H. pylori 700392 presented chemotaxis to arginine and sodium bicarbonate. H. pylori 700-tlpA::cat showed neither tlpA gene expression nor chemotaxis towards arginine and bicarbonate. Besides confirming that TlpA is a chemotactic receptor for arginine/bicarbonate in H. pylori, this study showed that tlpA gene expression is required for arginine/bicarbonate chemotaxis.

Mitochondria: role of citrulline and arginine supplementation in MELAS syndrome.

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El-Hattab, Ayman W; Emrick, Lisa T; Chanprasert, Sirisak; Craigen, William J; Scaglia, Fernando

2014-03-01

Mitochondria are found in all nucleated human cells and generate most of the cellular energy. Mitochondrial disorders result from dysfunctional mitochondria that are unable to generate sufficient ATP to meet the energy needs of various organs. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a frequent maternally inherited mitochondrial disorder. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS syndrome and results in impaired blood perfusion that contributes significantly to several complications including stroke-like episodes, myopathy, and lactic acidosis. Both arginine and citrulline act as NO precursors and their administration results in increased NO production and hence can potentially have therapeutic utility in MELAS syndrome. Citrulline raises NO production to a greater extent than arginine, therefore, citrulline may have a better therapeutic effect. Controlled studies assessing the effects of arginine or citrulline supplementation on different clinical aspects of MELAS syndrome are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Outcome And Arginine Serum of Acute Ischemic Stroke Patients Supplemented by Snakehead Fish Extract

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Pudjonarko, Dwi; Retnaningsih; Abidin, Zainal

2018-02-01

Background: Levels of arginine associated with clinical outcome in acute ischemic stroke (AIS). Arginine is a protein needed to synthesis nitric oxide (NO), a potential vasodilator and antioxidant. Snakehead fish is a source of protein which has antioxidant activity. Snakehead fish contains mineral, vitamin, and amino acids. One of the amino acids that were found quite high in snakehead fish extract is arginine. The aim of this study was done to determine the effect of snakehead fish extracts (SFE) on serum arginin levels and clinical outcome of AIS patients. Methods: It was double-blind randomized pretest-posttest control group design, with. AIS patients were divided into two groups i.e. snakehead fish extracts (SFE) and control. SFE group were administered 15 grams SFE for 7 days . Arginine serum levels and clinical outcome (measured by National Institute of Health Stroke Scale = NIHSS) were measured before and after treatment, other related factors were also analyzed in Logistic regression. Results: A total of 42 subjects who were performed random allocation as SFE or control group. There was no differences in subject characteristics between the two groups. There was a differences Δ arginine serum levels between SFE and control (33.6±19.95 μmol/L 0.3±2.51 μmol/L pgender factor that affected on improvement of NIHSS (OR=7; p=0,01). Conclusion: There is Clinical outcome improvement and enhancement of arginine serum levels in AIS patient with snakehead fish extract supplementation.

Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes

DEFF Research Database (Denmark)

Parlesak, Alexandr; Negrier, I.; Neveux, N.

2007-01-01

with arginine did not affect epithelial integrity, production of any of the cytokines investigated, or the amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with bacteria significantly enhanced...... the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation-associated cross...

The Effects of Pretreatment with Various Doses of L-Arginine on Cisplatin-Induced Nephropathy of Male Rats

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B Rasoulian

2016-09-01

Full Text Available Introduction: Cisplatin is a widely used anti-cancer drug, which its application is limited by nephrotoxicity. In this study, the effect of pretreatment with different l-arginine doses on Cisplatin-induced renal functional injury was investigated. Methods: 63 male rats were divided into 7 groups: In groups 3, 4, 5 and 6, 60 min before the Cisplatin injection (5mg/kg; L-Arginine with doses of 50,100,200 or 400mg/kg was injected, respectively. In group7, normal saline was injected before Cisplatin administration. In groups 1 and 2, normal saline was injected instead of Cisplatin. In group 2, 60min before normal saline injection, 400mg/kg L-Arginine was administered and in group1, instead of L-arginine, normal saline was injected too. Injections were intraperitoneal. 72h after Cisplatin injection, blood sampling and plasma separation were done. Urine sample was collected 24 hours before blood sampling by metabolic cage. The mean of plasma urea and creatinine levels and creatinine clearance (ml/day.kg and fractional excretion of Na (FENa, % were compared among different groups as renal functional parameters. Results: In comparison to group 7, L-arginine injection in a dose of 400mg/kg led to significant amelioration of all parameters. 200 mg/kg L-arginine administration led to significant decrease in plasma urea level and FENa. 100mg/kg L-arginine caused significant improvement in fractional excretion of sodium. L-arginine injection with 50mg/kg dose, significantly ameliorate all renal function tests instead of creatinine clearance. Conclusion: Pretreatment with L-arginine administration with 400 or 50 mg/kg doses, respectively, had the highest effect on reducing Cisplatin-induced nephropathy. L-arginine injection with intermediate doses i.e. 200 or 100 mg/kg had less effect in reducing Cisplatin-induced nephropathy and it needs more investigations.

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

DEFF Research Database (Denmark)

Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

2014-01-01

AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting...... responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar...

Deprivation of L-Arginine Induces Oxidative Stress Mediated Apoptosis in Leishmania donovani Promastigotes: Contribution of the Polyamine Pathway

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Mandal, Abhishek; Das, Sushmita; Roy, Saptarshi; Ghosh, Ayan Kumar; Sardar, Abul Hasan; Verma, Sudha; Saini, Savita; Singh, Ruby; Abhishek, Kumar; Kumar, Ajay; Mandal, Chitra; Das, Pradeep

2016-01-01

The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis. PMID:26808657

Reverse Transcriptase-Containing Particles Induced in Rous Sarcoma Virus-Transformed Rat Cells by Arginine Deprivation

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Kotler, Moshe; Weinberg, Eynat; Haspel, Osnat; Becker, Yechiel

1972-01-01

Incubation of rat cells transformed by Rous sarcoma virus (RSV) in an arginine-deficient medium resulted in accumulation of particles in the culture medium. Such particles did not appear when the transformed rat cells were incubated in a complete medium nor in the medium of primary rat cells which were incubated either in arginine-deficient or complete media. The particles which were released from the arginine-deprived transformed rat cells resemble C-type particles in their properties. These particles band in sucrose gradients at a density of 1.16 g/ml and contain 35S ribonucleic acid (RNA) molecules and a reverse transcriptase activity. Analysis of the cytoplasm of transformed and primary rat cells, deprived and undeprived of arginine, revealed the presence of reverse transcriptase-containing particles which banded in sucrose gradients at a density of 1.14 g/ml. These particles differed from the particles released into the medium by the arginine-deprived RSV-transformed rat cells. The deoxyribonucleic acid (DNA) molecules synthesized in vitro by the reverse transcriptase present in the particles isolated from the medium of arginine-deprived cells hybridized to RSV RNA, whereas the DNA synthesized by the cell-bound enzyme had no homology to RSV RNA. PMID:4116137

Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

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Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

2013-01-01

Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

Synthesis, characterization and behaviour of trans-bis (argininate) copper (II) to gamma radiation

International Nuclear Information System (INIS)

Pereira, A.B.

1984-01-01

The synthesis, the characterization and the behaviour to gamma radiation of trans-bis (argininate) copper (II) are presented. The synthesis is made from copper sulfate, sodium hydroxide and hydrochloride of L (+) arginine, in aqueous medium, and the characterization by infrared spectroscopy, visible and ultraviolet spectroscopy and elementary analysis. (C.G.C.)

Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

International Nuclear Information System (INIS)

Wagner, H.; Maier, V.; Franz, H.W.; Ulm Univ.; Ulm Univ.

1977-01-01

A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 μU/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 μU/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control. (orig.) [de

Improved method and its clinical application of a radioimmunoassay of arginine vasopressin in human serum

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Wagner, H; Maier, V; Franz, H W [Ulm Univ. (Germany, F.R.). Abt. Endokrinologie und Stoffwechsel; Ulm Univ. (Germany, F.R.). Zentrum fuer Innere Medizin und Kinderheilkunde; Ulm Univ. (Germany, F.R.). Sektion Nephrologie)

1977-05-01

A sensitive and specific double-antibody radioimmunoassay for measuring circulating levels of arginine vasopressin in human serum is described. It is possible to detect arginine vasopressin levels of 1 ..mu..U/ml serum without extraction procedure. Normal subjects were found to have 5.7 +- 4.4 ..mu..U/ml after a dehydration period of 12 hours. Water loading diminished arginine vasopressin concentrations while dehydration incrased it. Application of furosemide over a period of 14 days brought forth constant but not significant decreases. Subjects suffering from psychogenic polydipsia showed normal levels in spite of drinking 8-12 liters of water per day. Patients suffering from liver cirrhosis with ascites showed significantly higher arginine vasopressin levels, approaching normal values when ascites was under control.

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

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Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

2017-01-01

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

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Kuender D. Yang

2017-04-01

Full Text Available A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

Erythrocytes L-arginine y+ transporter inhibition by N-ethylmaleimide in ice-bath.

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Pinheiro da Costa, Bartira Ercília; de Almeida, Priscilla Barcellos; Conceição, Ioná Rosine; Antonello, Ivan Carlos Ferreira; d'Avila, Domingos O; Poli-de-Figueiredo, Carlos Eduardo

2010-11-01

Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

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Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

2016-03-01

This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

L-ARGININE PREVENTS METABOLIC EFFECTS OF HIGH GLUCOSE IN DIABETIC MICE

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West, Matthew B.; Ramana, Kota V.; Kaiserova, Karin; Srivastava, Satish K.; Bhatnagar, Aruni

2008-01-01

We tested the hypothesis that activation of the polyol pathway and protein kinase C (PKC) during diabetes is due to loss of NO. Our results show that after 4 weeks of streptozotocin-induced diabetes, treatment with L-arginine restored NO levels and prevented tissue accumulation of sorbitol in mice, which was accompanied by an increase in glutathiolation of aldose reductase. L-arginine treatment decreased superoxide generation in the aorta, total PKC activity and PKC-βII phosphorylation in the...

Structure of the C-terminal effector-binding domain of AhrC bound to its corepressor l-arginine

International Nuclear Information System (INIS)

Garnett, James A.; Baumberg, Simon; Stockley, Peter G.; Phillips, Simon E. V.

2007-01-01

The crystal structure of the C-terminal domain hexameric core of AhrC, with bound corepressor (l-arginine), has been solved at 1.95 Å resolution. Binding of l-arginine results in a rotation between the two trimers of the hexamer, leading to the activation of the DNA-binding state. The arginine repressor/activator protein (AhrC) from Bacillus subtilis belongs to a large family of multifunctional transcription factors that are involved in the regulation of bacterial arginine metabolism. AhrC interacts with operator sites in the promoters of arginine biosynthetic and catabolic operons, acting as a transcriptional repressor at biosynthetic sites and an activator of transcription at catabolic sites. AhrC is a hexamer of identical subunits, each having two domains. The C-terminal domains form the core of the protein and are involved in oligomerization and l-arginine binding. The N-terminal domains lie on the outside of the compact core and play a role in binding to 18 bp DNA operators called ARG boxes. The C-terminal domain of AhrC has been expressed, purified and characterized, and also crystallized as a hexamer with the bound corepressor l-arginine. Here, the crystal structure refined to 1.95 Å is presented

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

The effect of L-Arginine on the brain tissue of stressed rats

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Batoul Ebadi

2010-01-01

Full Text Available   Abstract  Introduction: This study was conducted to determine the possible beneficial results of L-arginine on prefrontal cortex of rats which impressed by immobilization stress to define the synchronous impression of stress and nitric oxide (NO on evolution of prefrontal cortex of rats after birth. Methods: Forty-eight one month, male Wistar rats were divided into two groups: stressed and non-stressed. L-Arginine (200 mg/kg as a NO synthase (NOS inducer and L-NAME (2O mg/kg were injected intraperitonealy (IP and 7- nitroindazde (25 mg/kg as non-specific was injected subcutaneously (S.C. for 4 weeks. The kind of stress was immobilization for 4 weeks, every other day. The brain was removed after this period and each brain divided into two parts in a coronal section manner. Anterior part used for histological studies with H&E staining and posterior part used for measurement of NO production using spectrophotometer at 540 nm wavelengh. Results: Statistical analysis of microscopic and light microscopic finding showed that thickness of prefrontal cortex and NO production were significantly decreased in stressed rats and especially in groups which received 7- nitroindazole and L-NAME and L-arginine could reverse these results. Discussion: According to this research, we could say that L-arginine decreases the cortical damages in stressed rats and 7-nitroindazole and L-NAME increase this damage in non-stressed group. Although in non stressed groups, L-arginine, L-NAME and 7- nitroindazole were all non-protective and damaging.

Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.

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El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

2016-04-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be

Biosynthesis of agmatine in isolated mitochondria and perfused rat liver: studies with 15N-labelled arginine

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2005-01-01

An important but unresolved question is whether mammalian mitochondria metabolize arginine to agmatine by the ADC (arginine decarboxylase) reaction. 15N-labelled arginine was used as a precursor to address this question and to determine the flux through the ADC reaction in isolated mitochondria obtained from rat liver. In addition, liver perfusion system was used to examine a possible action of insulin, glucagon or cAMP on a flux through the ADC reaction. In mitochondria and liver perfusion, 15N-labelled agmatine was generated from external 15N-labelled arginine. The production of 15N-labelled agmatine was time- and dose-dependent. The time-course of [U-15N4]agmatine formation from 2 mM [U-15N4]arginine was best fitted to a one-phase exponential curve with a production rate of approx. 29 pmol·min−1·(mg of protein)−1. Experiments with an increasing concentration (0– 40 mM) of [guanidino-15N2]arginine showed a Michaelis constant Km for arginine of 46 mM and a Vmax of 3.7 nmol·min−1·(mg of protein)−1 for flux through the ADC reaction. Experiments with broken mitochondria showed little changes in Vmax or Km values, suggesting that mitochondrial arginine uptake had little effect on the observed Vmax or Km values. Experiments with liver perfusion demonstrated that over 95% of the effluent agmatine was derived from perfusate [guanidino-15N2]arginine regardless of the experimental condition. However, the output of 15N-labelled agmatine (nmol·min−1·g−1) increased by approx. 2-fold (P<0.05) in perfusions with cAMP. The findings of the present study provide compelling evidence that mitochondrial ADC is present in the rat liver, and suggest that cAMP may stimulate flux through this pathway. PMID:15656789

Arginine promotes Proteus mirabilis motility and fitness by contributing to conservation of the proton gradient and proton motive force.

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Armbruster, Chelsie E; Hodges, Steven A; Smith, Sara N; Alteri, Christopher J; Mobley, Harry L T

2014-10-01

Swarming contributes to Proteus mirabilis pathogenicity by facilitating access to the catheterized urinary tract. We previously demonstrated that 0.1-20 mmol/L arginine promotes swarming on normally nonpermissive media and that putrescine biosynthesis is required for arginine-induced swarming. We also previously determined that arginine-induced swarming is pH dependent, indicating that the external proton concentration is critical for arginine-dependent effects on swarming. In this study, we utilized survival at pH 5 and motility as surrogates for measuring changes in the proton gradient (ΔpH) and proton motive force (μH(+) ) in response to arginine. We determined that arginine primarily contributes to ΔpH (and therefore μH(+) ) through the action of arginine decarboxylase (speA), independent of the role of this enzyme in putrescine biosynthesis. In addition to being required for motility, speA also contributed to fitness during infection. In conclusion, consumption of intracellular protons via arginine decarboxylase is one mechanism used by P. mirabilis to conserve ΔpH and μH(+) for motility. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Amniotic Fluid Arginine from Gestational Weeks 13 to 15 Is a Predictor of Birth Weight, Length, and Head Circumference

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Astrid Bjørke-Jenssen

2017-12-01

Full Text Available Arginine is a constituent of proteins and a precursor for polyamines and nitric oxide, and is essential for placentation, angiogenesis, and growth. Maternal plasma arginine concentrations are found to be lower in pregnancies complicated by fetal growth restriction, and arginine supplementation in later pregnancy is reported to increase birth weight. We measured arginine and the metabolites asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA in the amniotic fluid obtained in pregnancy weeks 13 to 15 from 363 pregnancies with a documented normal outcome and related the concentrations to birth weight, length, and head circumference. Arginine was higher in the amniotic fluid from female (mean 40.8 (SD 10.6 µmol/L compared to male fetuses (37.4 (SD 11.2 µmol/L, p = 0.003. Despite the gender difference, arginine in the amniotic fluid from gestational weeks 13–15 was the strongest predictor for birth weight, length, and head circumference. ADMA was a strong predictor for birth weight and length, SDMA for birth weight, while Arg/ADMA and Arg/SDMA only predicted head circumference in multiple linear regression models. Due to increased arginine demands, pregnancy is considered a state of relative arginine deficiency. Our findings reflect the importance of a good maternal arginine status in early pregnancy, an observation that should be evaluated in an intervention study.

Preparation of Simvastatin Hydrogel through Arginine Addition for Drug Delivery System

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Rosyida Niswati Fathmah

2018-01-01

Full Text Available Simvastatin is a lipid lowering agent which has been used recently as drug delivery system for stimulating bone regeneration. Because of low therapeutic efficacy and bioavailability, it is necessary to deliver simvastatin by local administration e.g. by hydrogel system. However, simvastatin has very poor solubility which restricts to prepare hydrogel formulation. The aim of this study is to improve solubility of simvastatin with arginine as co-solvent for developing a controlled released drug delivery system by loading simvastatin into gelatin hydrogel. The solubility study was performed by addition of an excess mass of simvastatin into the specified molar solutions of the arginine. All conical flasks were placed in a mechanical water bath shaker at the temperature of 25, 40, and 50 °C and shaken for a maximum period of 72 hours. The drug concentration was analyzed by UV/Visible spectroscopy at 238 nm. The hydrogel was prepared by a dehydrothermal method. The results showed that simvastatin solubility increases with increasing arginine concentrations and temperature. Characterizations showed a successful preparation of simvastatin-loaded gelatin hydrogel. The arginine simvastatin hydrogel and the gelatin hydrogel (as a blank exhibited a comparable swelling index (ca. 6.5. Furthermore, microparticles of the material show a narrow particle size distribution in the range between 150-250 μm.

Nutritional supplementation with arginine protects radiation-induced effects: an experimental study

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Pinto, Flavia Cristina Morone, E-mail: fcmorone@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco Jose Barcellos [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

2016-10-15

Purpose: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Methods: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. Results: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Conclusions: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine. (author)

Facilitation of peptide fibre formation by arginine-phosphate ...

Indian Academy of Sciences (India)

WINTEC

Peptide; self-assembly; arginine; microscopy. ... The latter property, in particular, observed in .... this process repeated till the gummy compound be- ..... micrograph of Congo red-stained image of individual peptide fibre from aged solution of 4.

Developmental changes of l-arginine transport at the blood-brain barrier in rats.

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Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

2018-05-01

l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

[l-arginine efficiency in MELAS syndrome. A case report].

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Moutaouakil, F; El Otmani, H; Fadel, H; Sefrioui, F; Slassi, I

2009-05-01

Mitochondrial encephalomyopathy lactic acidosis and stoke-like episodes (MELAS) is a rare neurodegenerative disease caused by mutations of mitochondrial DNA. We report the case of a 12-year-old child with MELAS syndrome who presented with recurrent migraine-like headache and sudden blindness suggesting stroke-like episodes. Furthermore, he developed progressive muscular impairment with bilateral hearing loss. Serum lactate and pyruvate levels were elevated and the muscle biopsy showed an aspect of red-ragged fibers with Gomori trichrome. Brain imaging showed calcifications of basal ganglia on the CT scan and a parieto-occipital high signal on diffusion-weighted MRI. A genetic analysis was not performed but the presence of hearing loss in the patient's mother was suggestive of maternal transmission. Stroke-like episodes in the form of migraine-like headache and blindness were the patient's major complaint and did not improve despite analgesic drugs. After oral administration of l-arginine at the dose of 0.4mg/kg per day, stroke-like symptoms totally and rapidly disappeared. The efficiency of l-arginine in stroke-like episodes was initially reported then confirmed in a controlled study. The pathophysiology of stoke-like episodes and the mechanisms underlying the action of l-arginine are discussed.

Altered Nitrogen Balance and Decreased Urea Excretion in Male Rats Fed Cafeteria Diet Are Related to Arginine Availability

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David Sabater

2014-01-01

rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway.

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Liang, Mingcai; Wang, Zhengxuan; Li, Hui; Cai, Liang; Pan, Jianghao; He, Hongjuan; Wu, Qiong; Tang, Yinzhao; Ma, Jiapei; Yang, Lin

2018-05-01

Arginine is a conditionally essential amino acid. To elucidate the influence of l-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with l-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities and glutathione (GSH) contents in the plasma and in the liver were uniformly enhanced with the increasing consumption of l-arginine, whereas the oxidative stress was effectively suppressed by l-arginine treatment. After 14 days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced by increasing l-arginine intake, resulting that the nuclear factor Nrf2 was activated. Upon activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, indicating an upward trend in antioxidant capacity uniformly with the increasing consumption of l-arginine. The present study demonstrates that the supplementation of l-arginine stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the availability of l-arginine is a critical factor to suppress oxidative stress and induce an endogenous antioxidant response. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

OpenAIRE

Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

1996-01-01

Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

Embryo Development and Post-Hatch Performances of Kampung Chicken by in Ovo Feeding of L-Arginine

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M. Azhar

2016-12-01

Full Text Available The research was conducted to evaluate embryo development, post-hatch performances, and growth rate of kampung chicken treated in-ovo feeding of L-Arginine. A total of 135 kampung chicken fertile eggs (weight 42-43 g were used and divided into 5 treatment groups of three replications. They were placed in the semi-automatic incubator. The first group was without in-ovo feeding (negative control; the second group was in-ovo feeding of saline 0.9% (positive control; the 3, 4, and 5 groups were in-ovo feeding of 0.5, 1.0, and 1.5% L-Arginine, respectively. In-ovo feeding of L-Arginine were injected into albumen on day 10 of incubation period using automatic syringe in the narrow end side of egg by inserting needle through a small hole at 10 mm depth. After hatching, all day old chicks were placed in floor pens (1 x 0.5 x 0.5 m accordance with the previous egg groups. The results showed that in-ovo feeding of L-Arginine increased weight and circumference of the embryo, but did not affect the length of embryo. In-ovo feeding of L-Arginine resulted in a higher body weight gain and a lower feed conversion even though feed intake was not significantly different compared to the control groups. The growth rate performance up to 6 weeks rearing increased significantly by increasing L-Arginine administration to 1.0%. It can be concluded that embryo development and post-hatch performances of kampung chicken were markedly increased by in-ovo feeding of L-arginine.

Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep with synchronized estrus.

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de Chávez, Julio Agustín Ruiz; Guzmán, Adrian; Zamora-Gutiérrez, Diana; Mendoza, Germán David; Melgoza, Luz María; Montes, Sergio; Rosales-Torres, Ana María

2015-08-01

The aim of the present study was to evaluate the effects of L-arginine-HCl supplementation on ovulation rate, fertility, prolificacy, and serum VEGF concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean body weight of 45 ± 3 kg and a mean body condition score (BCS) of 2.4 ± 0.28 were synchronized for estrus presentation with a progestin-containing sponge (20 mg Chronogest® CR) for 9 days plus PGF2-α (Lutalyse; Pfizer, USA) on day 7 after the insertion of the sponge. The ewes were divided into two groups; i.e., a control group (n = 15) that was fed on the native pasture (basal diet) and an L-arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl from day 5 of the sponge insertion until day 25 after mating plus the basal diet. The L-arginine-HCl was administered daily via an esophageal probe between days 5 and 9 of the synchronization protocol and every third day subsequently. Blood samples were drawn from the jugular vein every 6 days throughout the entire experimental period. The results revealed that the L-arginine-HCl supplementation increased fertility during the synchronized estrus (P = 0.05). However, no effects were observed on the final BCS (P = 0.78), estrus presentation (P = 0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF concentration. In conclusion, L-arginine-HCl supplementation during the period used in this study increased fertility in sheep with synchronized estrus possibly due to improved embryo-fetal survival during early pregnancy.

Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

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María R. Alberto

2012-03-01

Full Text Available The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC, found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively. ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds.

Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

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Xu, Meijuan; Qin, Jingru; Rao, Zhiming; You, Hengyi; Zhang, Xian; Yang, Taowei; Wang, Xiaoyuan; Xu, Zhenghong

2016-01-19

Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L-arginine

Evidence for arginine as the endogenous precursor of necines in heliotropium.

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Birecka, H; Birecki, M; Frohlich, M W

1987-05-01

In pyrrolizidine alkaloid-bearing Heliotropium angiospermum and H. indicum shoots exposed, in the light, to (14)C-labeled CO(2) for 44 hours, the incorporation of (14)C into 1,2-epoxy-1-hydroxymethylpyrrolizidine and retronecine amounted to 0.23 and 0.15%, respectively, of the total carbon assimilated. Treatment of the shoots with alpha-dl-difluoromethylornithine, the specific ornithine decarboxylase inhibitor, at 1 to 2 millimolar had no effect on (14)C incorporation into the necines. In contrast, alpha-dl-difluoromethylarginine, the specific arginine decarboxylase inhibitor, prevented the incorporation of (14)C into the necines of both species; the inhibitor did not affect the absolute incorporation of (14)C from exogenous [1,4-(14)C] putrescine in either species. Thus, arginine is the only apparent endogenous precursor of the putrescine channeled into pyrrolizidines, at least in these two Heliotropium species that exhibited a relatively much higher in vitro activity of arginine decarboxylase than of ornithine decarboxylase. However, within 28 hours after administration, not only exogenous l-[5-(14)C]arginine, but also exogenous l-[5-(14)C]ornithine exhibited significant incorporation of their label into the necines, incorporation that could be partially prevented by both inhibitors. Neither inhibitor affected the rates of (14)C-labeled CO(2) assimilation, transformation of labeled assimilates into ethanol-insoluble compounds, or the very high degree of conversion of the introduced amino acids into other compounds. Methodology related to alkaloid biosynthetic studies is discussed.

Growth and dielectric, mechanical, thermal and etching studies of an organic nonlinear optical L-arginine trifluoroacetate (LATF) single crystal

International Nuclear Information System (INIS)

Arjunan, S.; Mohan Kumar, R.; Mohan, R.; Jayavel, R.

2008-01-01

L-arginine trifluoroacetate, an organic nonlinear optical material, has been synthesized from aqueous solution. Bulk single crystal of dimension 57 mm x 5 mm x 3 mm has been grown by temperature lowering technique. Powder X-ray diffraction studies confirmed the monoclinic structure of the grown L-arginine trifluoroacetate crystal. Linear optical property of the grown crystal has been studied by UV-vis spectrum. Dielectric response of the L-arginine trifluoroacetate crystal was analysed for different frequencies and temperatures in detail. Microhardness study on the sample reveals that the crystal possesses relatively higher hardness compared to many organic crystals. Thermal analyses confirmed that the L-arginine trifluoroacetate material is thermally stable upto 212 deg. C. The etching studies have been performed to assess the perfection of the L-arginine trifluoroacetate crystal. Kurtz powder second harmonic generation test confirms the nonlinear optical properties of the as-grown L-arginine trifluoroacetate crystal

Synthesis of specific deuterium labeled tyrosine and phenylalanine derivatives and their use in the total synthesis of [8-arginine]vasopressin derivatives: the separation of diastereomeric [8-arginine]vasopressin derivatives by partition chromatography

International Nuclear Information System (INIS)

Yamamoto, D.M.; Upson, D.A.; Linn, D.K.; Hruby, V.J.

1977-01-01

Derivatives of tyrosine specifically deuterated at the α carbon ([α- 2 H 1 ]tyrosine) and at both the α and β carbons ([α,β,β- 2 H 3 ]tyrosine) and a derivative of phenylalanine specifically deuterated at the α carbon ([α- 2 H 1 ]phenylalanine) have been synthesized in high yield. These labeled compounds have been resolved enzymatically, and the enantiomers and racemates have been converted to N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. The protected derivatives as well as specifically deuterated derivatives of S-benzylcysteine and of glycine were used to prepare specifically deuterated analogues of [8-arginine] vasopressin using solid phase peptide procedures. The use of improved synthetic procedures resulted in considerable improvements in the yields of [8-arginine]vasopressin compared with previous reports. In addition, new solvent systems for partition chromatography purification of [8-arginine]vasopressin on Sephadex were developed which allowed a facile one-step separation of diastereomers of [8-arginine]vasopressin containing a racemic amino acid at either the 1-hemicystine or the 2-tyrosine positions of the hormone

Tracking the behavior of Maillard browning in lysine/arginine-sugar model systems under high hydrostatic pressure.

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Ma, Xiao-Juan; Gao, Jin-Yan; Tong, Ping; Li, Xin; Chen, Hong-Bing

2017-12-01

High-pressure processing is gaining popularity in the food industry. However, its effect on the Maillard reaction during high-pressure-assisted pasteurization and sterilization is not well documented. This study aimed to investigate the effects of high hydrostatic pressure on the Maillard reaction during these processes using amino acid (lysine or arginine)-sugar (glucose or fructose) solution models. High pressure retarded the intermediate and final stages of the Maillard reaction in the lysine-sugar model. For the lysine-glucose model, the degradation rate of Amadori compounds was decelerated, while acceleration was observed in the arginine-sugar model. Increased temperature not only accelerated the Maillard reaction over time but also formed fluorescent compounds with different emission wavelengths. Lysine reacted with the sugars more readily than arginine under the same conditions. In addition, it was easier for lysine to react with glucose, whereas arginine reacted more readily with fructose under high pressure. High pressure exerts different effects on lysine-sugar and arginine-sugar models. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

PRMT1-mediated arginine methylation controls ATXN2L localization

Energy Technology Data Exchange (ETDEWEB)

Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

2015-05-15

Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

A UV-induced mutation in neurospora that affects translational regulation in response to arginine

International Nuclear Information System (INIS)

Freitag, M.; Dighde, N.; Sachs, M.S.

1996-01-01

The Neurospora crassa arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript's 5' region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and arg-2 genes; the other, altered expression of arg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5' region of the arg-2-hph gene using PCR Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFs suggest common elements in translational control mechanisms

PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core.

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Barbora Lubyova

Full Text Available In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc protein and dimethylates arginine residues within the arginine-rich domain (ARD of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI and R156 (outside ARDs were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs, arginine methylation and ubiquitination.

Competitive metabolism of L-arginine: arginase as a therapeutic target in asthma☆

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Bratt, Jennifer M.; Zeki, Amir A.; Last, Jerold A.; Kenyon, Nicholas J.

2011-01-01

Exhaled breath nitric oxide (NO) is an accepted asthma biomarker. Lung concentrations of NO and its amino acid precursor, L-arginine, are regulated by the relative expressions of the NO synthase (NOS) and arginase isoforms. Increased expression of arginase I and NOS2 occurs in murine models of allergic asthma and in biopsies of asthmatic airways. Although clinical trials involving the inhibition of NO-producing enzymes have shown mixed results, small molecule arginase inhibitors have shown potential as a therapeutic intervention in animal and cell culture models. Their transition to clinical trials is hampered by concerns regarding their safety and potential toxicity. In this review, we discuss the paradigm of arginase and NOS competition for their substrate L-arginine in the asthmatic airway. We address the functional role of L-arginine in inflammation and the potential role of arginase inhibitors as therapeutics. PMID:23554705

Calcium Sensing Receptor Mutations Implicated in Pancreatitis and Idiopathic Epilepsy Syndrome Disrupt an Arginine-rich Retention Motif

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Stepanchick, Ann; McKenna, Jennifer; McGovern, Olivia; Huang, Ying; Breitwieser, Gerda E.

2010-01-01

Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended arginine-rich region in the proximal carboxyl terminus. Arginine-rich motifs mediate endoplasmic reticulum retention and/or retrieval of multisubunit proteins so we asked whether these mutations, R886P, R896H or R898Q, altered CaSR targeting to the plasma membrane. Targeting was enhanced by all three mutations, and Ca2+-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q. To define the role of the extended arginine-rich region in CaSR trafficking, we independently determined the contributions of R890/R891 and/or R896/K897/R898 motifs by mutation to alanine. Disruption of the motif(s) significantly increased surface expression and function relative to wt CaSR. The arginine-rich region is flanked by phosphorylation sites at S892 (protein kinase C) and S899 (protein kinase A). The phosphorylation state of S899 regulated recognition of the arginine-rich region; S899D showed increased surface localization. CaSR assembles in the endoplasmic reticulum as a covalent disulfide-linked dimer and we determined whether retention requires the presence of arginine-rich regions in both subunits. A single arginine-rich region within the dimer was sufficient to confer intracellular retention comparable to wt CaSR. We have identified an extended arginine-rich region in the proximal carboxyl terminus of CaSR (residues R890 - R898) which fosters intracellular retention of CaSR and is regulated by phosphorylation. Mutation(s) identified in chronic pancreatitis and idiopathic epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely contributing to the altered Ca2+ signaling characteristic of these diseases. PMID:20798521

Temporal Lob Epilepsi'sinde L-Arginine ve CaEDTA'nın Etkileri

OpenAIRE

NOYAN, Behzat

2005-01-01

Bu çalışmada, bir nitrik oksit (NO-) prekürsörü olan L-Arginine ve bir ekstrasellüler çinko şelatörü olan CaEDTA'nın pilokarpine HCl ile oluşturulan kısa süreli epileptik nöbet üzerine etkileri araştırıldı. Deney, nöbet kontrol (serum fizyolojik 10 µl, i.c.v., ve sonra 380 mg/kg pilokarpine HCl i.p.), L-Arginine (150 µg/10 µl, i.c.v.), CaEDTA (100 mM, 10 µl, i.c.v.), L-Arginine+CaEDTA olmak üzere 4 gruptan oluştu. Enjeksiyonlardan sonra iki saat boyunca nöbet davranışları gözlemlenen ...

Transcriptome analysis shows activation of the arginine deiminase pathway in Lactococcus lactis as a response to ethanol stress.

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Díez, Lorena; Solopova, Ana; Fernández-Pérez, Rocío; González, Miriam; Tenorio, Carmen; Kuipers, Oscar P; Ruiz-Larrea, Fernanda

2017-09-18

This paper describes the molecular response of Lactococcus lactis NZ9700 to ethanol. This strain is a well-known nisin producer and a lactic acid bacteria (LAB) model strain. Global transcriptome profiling using DNA microarrays demonstrated a bacterial adaptive response to the presence of 2% ethanol in the culture broth and differential expression of 67 genes. The highest up-regulation was detected for those genes involved in arginine degradation through the arginine deiminase (ADI) pathway (20-40 fold up-regulation). The metabolic responses to ethanol of wild type L. lactis strains were studied and compared to those of regulator-deletion mutants MG∆argR and MG∆ahrC. The results showed that in the presence of 2% ethanol those strains with an active ADI pathway reached higher growth rates when arginine was available in the culture broth than in absence of arginine. In a chemically defined medium strains with an active ADI pathway consumed arginine and produced ornithine in the presence of 2% ethanol, hence corroborating that arginine catabolism is involved in the bacterial response to ethanol. This is the first study of the L. lactis response to ethanol stress to demonstrate the relevance of arginine catabolism for bacterial adaptation and survival in an ethanol containing medium. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of arginine metabolic pathway during embryogenesis and germination in maritime pine (Pinus pinaster Ait.).

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Llebrés, María-Teresa; Pascual, María-Belén; Debille, Sandrine; Trontin, Jean-François; Harvengt, Luc; Avila, Concepción; Cánovas, Francisco M

2018-03-01

Vegetative propagation through somatic embryogenesis is critical in conifer biotechnology towards multivarietal forestry that uses elite varieties to cope with environmental and socio-economic issues. An important and still sub-optimal process during in vitro maturation of somatic embryos (SE) is the biosynthesis and deposition of storage proteins, which are rich in amino acids with high nitrogen (N) content, such as arginine. Mobilization of these N-rich proteins is essential for the germination and production of vigorous somatic seedlings. Somatic embryos accumulate lower levels of N reserves than zygotic embryos (ZE) at a similar stage of development. To understand the molecular basis for this difference, the arginine metabolic pathway has been characterized in maritime pine (Pinus pinaster Ait.). The genes involved in arginine metabolism have been identified and GFP-fusion constructs were used to locate the enzymes in different cellular compartments and clarify their metabolic roles during embryogenesis and germination. Analysis of gene expression during somatic embryo maturation revealed high levels of transcripts for genes involved in the biosynthesis and metabolic utilization of arginine. By contrast, enhanced expression levels were only observed during the last stages of maturation and germination of ZE, consistent with the adequate accumulation and mobilization of protein reserves. These results suggest that arginine metabolism is unbalanced in SE (simultaneous biosynthesis and degradation of arginine) and could explain the lower accumulation of storage proteins observed during the late stages of somatic embryogenesis.

l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

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Abhishek Mandal

2017-07-01

Full Text Available The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL, depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important

Exogenous L-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

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Garcia, Vinicius P; Rocha, Helena N M; Silva, Gustavo M.

2016-01-01

Aims Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective L-arginine-NO pathway. Exogenous L-arginine improves endothelial function to prevent the onset of cardiovascular...... disease, but the mechanism by which this is accomplished remains unclear. We determined the effects of exogenous L-arginine infusion on vascular biomarkers in patients with hypertension. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group...... biomarkers between groups during the saline infusion (P > 0.05). Significance Exogenous L-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension....

L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

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Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

2009-02-01

The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

PRmePRed: A protein arginine methylation prediction tool.

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Pawan Kumar

Full Text Available Protein methylation is an important Post-Translational Modification (PTMs of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results. This motivated us to perform a comprehensive data analysis and appraisal of features relevant in the context of biological significance, that led to the development of a prediction tool PRmePRed with better performance. The PRmePRed perform reasonably well with an accuracy of 84.10%, 82.38% sensitivity, 83.77% specificity, and Matthew's correlation coefficient of 66.20% in 10-fold cross-validation. PRmePRed is freely available at http://bioinfo.icgeb.res.in/PRmePRed/.

Spray drying of poorly soluble drugs from aqueous arginine solution.

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Ojarinta, Rami; Lerminiaux, Louise; Laitinen, Riikka

2017-10-30

Co-amorphous drug-amino acid mixtures have shown potential for improving the solid-state stability and dissolution behavior of amorphous drugs. In previous studies, however these mixtures have been produced mainly with small-scale preparation methods, or with methods that have required the use of organic solvents or other dissolution enhancers. In the present study, co-amorphous ibuprofen-arginine and indomethacin-arginine mixtures were spray dried from water. The mixtures were prepared at two drug-arginine molar ratios (1:1 and 1:2). The properties of the prepared mixtures were investigated with differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and a 24h, non-sink, dissolution study. All mixtures exhibited a single glass transition temperature (T g ), evidence of the formation of homogenous single-phase systems. Fourier transform infrared spectroscopy revealed strong interactions (mainly salt formation) that account for the positive deviation between measured and estimated T g values. No crystallization was observed during a 1-year stability study in either 1:1 or 1:2 mixtures, but in the presence of moisture, handling difficulties were encountered. The formation of co-amorphous salts led to improved dissolution characteristics when compared to the corresponding physical mixtures or to pure crystalline drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

The control of fruiting body formation in the ascomycete Sordaria macrospora Auersw. by arginine and biotin: a two-factor analysis.

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Molowitz, R; Bahn, M; Hock, B

1976-01-01

Fruiting body formation of Sordaria macrospora Auersw. is controlled by L-arginine and biotin when the fungus is grown on a synthetic nutrient medium containing optimal concentrations of fructose, KNO3, KH2PO4, MgSO4, and ZnSO4. Arginine and biotin operate in very low concentrations which exclude unspecific nutrient effects. In spite of the complicated interactions of arginine and biotin which are shown qualitatively (Figs. 3 and 4a) and quantitatively (Figs. 2 and 4b), the following conclusions are reached: 1. In the absence of biotin, the development of Sordaria macrospora is blocked at the stage of small protoperithecia. The external addition of biotin (optimal concentration: 3-12 μg/l) allows the formation of fertile fruiting bodies. This effect cannot be imitated by arginine. The biotin effect is discussed in connection with stimulated RNA synthesis.-2. The developmental velocity is influenced by the external addition of arginine. Without arginine but at permissible biotin concentrations, the total life cycle takes about 10 days, in the presence of arginine (1 mM), however, about 6 days.-3. The hyphal density, as well as the total number of fruiting bodies being produced, is controlled in a similar manner by biotin and arginine. The induction of fruiting body formation obviously takes place after the transgression of a critical hyphal density.

Arginine vasopressin stimulates phosphoinositide turnover in an enriched rat Leydig cell preparation

DEFF Research Database (Denmark)

Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

1989-01-01

An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol and phosphatidyl......An enriched rat Leydig cell preparation was preincubated with [C]arachidonic acid. Stimulation of the cells with arginine vasopressin (AVP) (1 µM) for 2 min caused a significant increase in labelled phosphatidic acid and a significant fall in radioactivity in phosphatidylinositol...

Soil CO2 evolution: Response from arginine additions

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Short-term response of soil C mineralization following drying/rewetting has been proposed as an indicator of soil microbial activity. Houston Black clay was amended with four rates of arginine to vary microbial response and keep other soil properties constant. The evolution of CO2 during one and thr...

Glutamine-enriched enteral diet increases renal arginine production

NARCIS (Netherlands)

Houdijk, A. P.; van Leeuwen, P. A.; Teerlink, T.; FLINKERBUSCH, E. L.; Boermeester, M. A.; Sauerwein, H. P.; Wesdorp, R. I.

1994-01-01

Arginine (Arg) is generated in the kidney by the conversion of circulating citrulline. The most important source for circulating citrulline is the metabolism of glutamine (Gln) by the gut. In this study, we investigated the influence of an enteral diet enriched with Gln on renal Arg synthesis in the

Evidence for Arginine as the Endogenous Precursor of Necines in Heliotropium1

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Birecka, Helena; Birecki, Mieczyslaw; Frohlich, M. W.

1987-01-01

In pyrrolizidine alkaloid-bearing Heliotropium angiospermum and H. indicum shoots exposed, in the light, to 14C-labeled CO2 for 44 hours, the incorporation of 14C into 1,2-epoxy-1-hydroxymethylpyrrolizidine and retronecine amounted to 0.23 and 0.15%, respectively, of the total carbon assimilated. Treatment of the shoots with α-dl-difluoromethylornithine, the specific ornithine decarboxylase inhibitor, at 1 to 2 millimolar had no effect on 14C incorporation into the necines. In contrast, α-dl-difluoromethylarginine, the specific arginine decarboxylase inhibitor, prevented the incorporation of 14C into the necines of both species; the inhibitor did not affect the absolute incorporation of 14C from exogenous [1,4-14C] putrescine in either species. Thus, arginine is the only apparent endogenous precursor of the putrescine channeled into pyrrolizidines, at least in these two Heliotropium species that exhibited a relatively much higher in vitro activity of arginine decarboxylase than of ornithine decarboxylase. However, within 28 hours after administration, not only exogenous l-[5-14C]arginine, but also exogenous l-[5-14C]ornithine exhibited significant incorporation of their label into the necines, incorporation that could be partially prevented by both inhibitors. Neither inhibitor affected the rates of 14C-labeled CO2 assimilation, transformation of labeled assimilates into ethanol-insoluble compounds, or the very high degree of conversion of the introduced amino acids into other compounds. Methodology related to alkaloid biosynthetic studies is discussed. PMID:16665402

L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

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L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at th...

Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

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Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

2011-07-01

ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

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Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2016-11-01

Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

Effects of Arginine Supplementation on Amino Acid Profiles in Blood and Tissues in Fed and Overnight-Fasted Rats

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Milan Holecek

2016-04-01

Full Text Available Chronic arginine intake is believed to have favorable effects on the body. However, it might be hypothesized that excessive consumption of an individual amino acid exerts adverse effects on distribution and metabolism of other amino acids. We evaluated the effect of chronic intake of arginine on amino acid concentrations in blood plasma, liver, kidneys, and soleus and extensor digitorum longus muscles. Rats were fed a standard diet or a high-arginine diet (HAD for two months. Half of the animals in each group were sacrificed in the fed state, and the other half after fasting overnight. HAD increased blood plasma concentrations of urea, creatinine, arginine, and ornithine and decreased most other amino acids. Arginine and ornithine also increased in muscles and kidneys; an increase of lysine was observed in both muscle types. Methionine, phenylalanine, threonine, asparagine, glycine, serine, and taurine decreased in most tissues of HAD fed animals. Most of the effects of HAD disappeared after overnight fasting. It is concluded that (i enhanced dietary arginine intake alters distribution of almost all amino acids; and (ii to attain a better assessment of the effects of various nutritional interventions, an appropriate number of biochemical measurements must be performed in both postprandial and postabsorptive states.

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters.

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Rathmacher, J A; Nissen, S; Panton, L; Clark, R H; Eubanks May, P; Barber, A E; D'Olimpio, J; Abumrad, N N

2004-01-01

Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day. Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation. These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

Insight on an arginine synthesis metabolon from the tetrameric structure of yeast acetylglutamate kinase.

Science.gov (United States)

de Cima, Sergio; Gil-Ortiz, Fernando; Crabeel, Marjolaine; Fita, Ignacio; Rubio, Vicente

2012-01-01

N-acetyl-L-glutamate kinase (NAGK) catalyzes the second, generally controlling, step of arginine biosynthesis. In yeasts, NAGK exists either alone or forming a metabolon with N-acetyl-L-glutamate synthase (NAGS), which catalyzes the first step and exists only within the metabolon. Yeast NAGK (yNAGK) has, in addition to the amino acid kinase (AAK) domain found in other NAGKs, a ~150-residue C-terminal domain of unclear significance belonging to the DUF619 domain family. We deleted this domain, proving that it stabilizes yNAGK, slows catalysis and modulates feed-back inhibition by arginine. We determined the crystal structures of both the DUF619 domain-lacking yNAGK, ligand-free as well as complexed with acetylglutamate or acetylglutamate and arginine, and of complete mature yNAGK. While all other known arginine-inhibitable NAGKs are doughnut-like hexameric trimers of dimers of AAK domains, yNAGK has as central structure a flat tetramer formed by two dimers of AAK domains. These dimers differ from canonical AAK dimers in the -110° rotation of one subunit with respect to the other. In the hexameric enzymes, an N-terminal extension, found in all arginine-inhibitable NAGKs, forms a protruding helix that interlaces the dimers. In yNAGK, however, it conforms a two-helix platform that mediates interdimeric interactions. Arginine appears to freeze an open inactive AAK domain conformation. In the complete yNAGK structure, two pairs of DUF619 domains flank the AAK domain tetramer, providing a mechanism for the DUF619 domain modulatory functions. The DUF619 domain exhibits the histone acetyltransferase fold, resembling the catalytic domain of bacterial NAGS. However, the putative acetyl CoA site is blocked, explaining the lack of NAGS activity of yNAGK. We conclude that the tetrameric architecture is an adaptation to metabolon formation and propose an organization for this metabolon, suggesting that yNAGK may be a good model also for yeast and human NAGSs.

Insight on an arginine synthesis metabolon from the tetrameric structure of yeast acetylglutamate kinase.

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Sergio de Cima

Full Text Available N-acetyl-L-glutamate kinase (NAGK catalyzes the second, generally controlling, step of arginine biosynthesis. In yeasts, NAGK exists either alone or forming a metabolon with N-acetyl-L-glutamate synthase (NAGS, which catalyzes the first step and exists only within the metabolon. Yeast NAGK (yNAGK has, in addition to the amino acid kinase (AAK domain found in other NAGKs, a ~150-residue C-terminal domain of unclear significance belonging to the DUF619 domain family. We deleted this domain, proving that it stabilizes yNAGK, slows catalysis and modulates feed-back inhibition by arginine. We determined the crystal structures of both the DUF619 domain-lacking yNAGK, ligand-free as well as complexed with acetylglutamate or acetylglutamate and arginine, and of complete mature yNAGK. While all other known arginine-inhibitable NAGKs are doughnut-like hexameric trimers of dimers of AAK domains, yNAGK has as central structure a flat tetramer formed by two dimers of AAK domains. These dimers differ from canonical AAK dimers in the -110° rotation of one subunit with respect to the other. In the hexameric enzymes, an N-terminal extension, found in all arginine-inhibitable NAGKs, forms a protruding helix that interlaces the dimers. In yNAGK, however, it conforms a two-helix platform that mediates interdimeric interactions. Arginine appears to freeze an open inactive AAK domain conformation. In the complete yNAGK structure, two pairs of DUF619 domains flank the AAK domain tetramer, providing a mechanism for the DUF619 domain modulatory functions. The DUF619 domain exhibits the histone acetyltransferase fold, resembling the catalytic domain of bacterial NAGS. However, the putative acetyl CoA site is blocked, explaining the lack of NAGS activity of yNAGK. We conclude that the tetrameric architecture is an adaptation to metabolon formation and propose an organization for this metabolon, suggesting that yNAGK may be a good model also for yeast and human NAGSs.

Allevation of Oxidative Damages Induced by Salinity in Cress (Lepidium sativum by Pretreating with Arginine

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E Asadi karam

2015-05-01

Full Text Available Salinity is one of the main stresses that have negative effectcs on seedling growth, and plant production. It inhibits growth of plants through disturbance of the balance between production of ROS and antioxidant defense mechanism which results in oxidative stress. Because, arginine is a vital regulator of physiological and developmental processes the effect of different concentrations of arginine pretreatment of the plant on alleviation of oxidative stress induced by salt 50 and 100Mm NaCl was investigated. Arginine pretreatment increased chlorophyll a, b, carotenoid and seedling growth under salinity condition. Results also showed that salt stress increased proline, protein, H2O2, soluble sugar and the activity of ascorbate peroxidase, guaiacol peroxidase and catalase. Pretreatment of plants with Arg reduced proline, soluble sugar, H2O2 and antioxidant enzymes activity content significantly. The conclusion is that in garden cress plants, pretreatment with concentration of 5 µM and 10 μM arginine may protect cress under salinity stress, probably through the contracting with ROS and or induction of anti-oxidative enzymes

The Hydrophobic Region of the DmsA Twin-Arginine Leader Peptide Determines Specificity with Chaperone DmsD

OpenAIRE

Winstone, Tara M. L.; Tran, Vy A.; Turner, Raymond J.

2013-01-01

The system specific chaperone DmsD plays a role in the maturation of the catalytic subunit of dimethyl sulfoxide (DMSO) reductase, DmsA. Pre-DmsA contains a 45-amino acid twin-arginine leader peptide that is important for targeting and translocation of folded and cofactor-loaded DmsA by the twin-arginine translocase. DmsD has previously been shown to interact with the complete twin-arginine leader peptide of DmsA. In this study, isothermal titration calorimetry was used to investigate the the...

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease

DEFF Research Database (Denmark)

Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

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Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

2017-02-01

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy–enriched enteral formula12345

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de Betue, Carlijn TI; Joosten, Koen FM; Deutz, Nicolaas EP; Vreugdenhil, Anita CE; van Waardenburg, Dick A

2013-01-01

Background: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy–enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. Objective: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. Design: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. Results: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 μmol · kg−1 · h−1; S-formula: 130 ± 53 μmol · kg−1 · h−1; P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 μmol · kg−1 · h−1; S-formula: 0.84 ± 0.36 μmol · kg−1 · h−1; P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. Conclusion: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515. PMID:23945723

Arginase and Arginine Decarboxylase - Where Do the Putative Gate Keepers of Polyamine Synthesis Reside in Rat Brain?

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Daniela Peters

Full Text Available Polyamines are important regulators of basal cellular functions but also subserve highly specific tasks in the mammalian brain. With this respect, polyamines and the synthesizing and degrading enzymes are clearly differentially distributed in neurons versus glial cells and also in different brain areas. The synthesis of the diamine putrescine may be driven via two different pathways. In the "classical" pathway urea and carbon dioxide are removed from arginine by arginase and ornithine decarboxylase. The alternative pathway, first removing carbon dioxide by arginine decarboxlyase and then urea by agmatinase, may serve the same purpose. Furthermore, the intermediate product of the alternative pathway, agmatine, is an endogenous ligand for imidazoline receptors and may serve as a neurotransmitter. In order to evaluate and compare the expression patterns of the two gate keeper enzymes arginase and arginine decarboxylase, we generated polyclonal, monospecific antibodies against arginase-1 and arginine decarboxylase. Using these tools, we immunocytochemically screened the rat brain and compared the expression patterns of both enzymes in several brain areas on the regional, cellular and subcellular level. In contrast to other enzymes of the polyamine pathway, arginine decarboxylase and arginase are both constitutively and widely expressed in rat brain neurons. In cerebral cortex and hippocampus, principal neurons and putative interneurons were clearly labeled for both enzymes. Labeling, however, was strikingly different in these neurons with respect to the subcellular localization of the enzymes. While with antibodies against arginine decarboxylase the immunosignal was distributed throughout the cytoplasm, arginase-like immunoreactivity was preferentially localized to Golgi stacks. Given the apparent congruence of arginase and arginine decarboxylase distribution with respect to certain cell populations, it seems likely that the synthesis of agmatine

Heritability and genetic variance for citrulline, arginine and lycopene content in a diverse set of watermelon cultigens

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Citrulline, arginine, and lycopene are naturally occurring compounds found in watermelon, Citrullus lanatus (Thumb) Matsum & Nakai, with beneficial effects on plant growth and human health. This study evaluated seven commercial cultivars and one breeding line for citrulline, arginine, and lycopene c...

Association of arginine vasopressin receptor 1a gene polymorphisms with hepatorenal syndrome

International Nuclear Information System (INIS)

Wang, C.; Luo, X.; Ye, J.; Liu, S.; Miu, L.; Bao, J.; Wang, F.; Yu, Z.

2017-01-01

To assess the association of arginine vasopressin receptor 1a gene single nucleotide polymorphisms with type I hepatorenal syndrome. Methods: The case-control study was conducted at the Hangzhou City Xixi Hospital, Hangzhou, China, from January 2012 to June 2014, and comprised patients with type I hepatorenal syndrome and individuals with cirrhosis who acted as the control group. Arginine vasopressin receptor 1a gene rs113481894 locus single nucleotide polymorphisms were analysed by high-resolution melting methods. Statistical analysis was performed using SPSS 17. Results: Of the 60 participants, 28(46.7%) were in the hepatorenal syndrome group and 32(53.3%) were controls. The mean age was 42.21+-11.30years in the hepatorenal syndrome group and 43.69+-12.60 in the control group (p=0.64). Mean total bilirubin, albumin and prothrombin activity levels were 154.76+-51.58, 49.30+-24.67 and 33.42+-3.69 in the hepatorenal syndrome group compared to 181.26+-64.46, 41.78+-17.52 and 32.98+-4.81 among controls (p=0.09, p=0.18 and p=0.70). Statistically significant differences were found in the distributions of arginine vasopressin receptor 1a gene rs113481894 locus T allele between type I hepatorenal syndrome patients and the control group (odds ratio= 2.230; p= 0.040). Conclusion: T allele located at arginine vasopressin receptor 1a receptor promoter rs113481894 locus may be associated with the pathogenesis of type I hepatorenal syndrome. (author)

The Effects Of L-Arginine And L-Name On Coronary Flow And Oxidative Stress In Isolated Rat Hearts

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Sobot Tanja

2015-12-01

Full Text Available The aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g. Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O. The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker, superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances. The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol and L-arginine (1 mmol + L-NAME (30 μmol. The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation

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Amal Abdussalam Ali A. Hmaid

2018-03-01

Full Text Available Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C or cold (4 ± 1 °C and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis. Keywords: Cardiomyocyte, Cardiac hypertrophy, l-Arginine, l-NAME, Myocardium

Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis

DEFF Research Database (Denmark)

Schön, T; Elias, D; Moges, F

2003-01-01

Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal NO produ......Nitric oxide (NO) is involved in the host defence against tuberculosis (TB). Patients with TB exhibit increased catabolism and reduced energy intake. Thus the hypothesis for this study was that restoring a relative deficiency in the amino acid arginine, the substrate for mycobactericidal...... virus-negative patients with active tuberculosis, most likely mediated by increased production of nitric oxide....

L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

International Nuclear Information System (INIS)

Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

2012-01-01

Highlights: ► L-Arginine treatment reduced the metabolic disturbances in diabetic animals. ► Antioxidant marker proteins were found high in myocardium by L-arginine treatment. ► Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. ► L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. ► Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg −1 body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be

L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

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Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

2012-11-23

Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

Arginine-dependent acid resistance in Salmonella enterica serovar Typhimurium

NARCIS (Netherlands)

Kieboom, J.; Abee, T.

2006-01-01

Salmonella enterica serovar Typhimurium does not survive a pH 2.5 acid challenge under conditions similar to those used for Escherichia coli (J. W. Foster, Nat. Rev. Microbiol. 2:898-907, 2004). Here, we provide evidence that S. enterica serovar Typhimurium can display arginine-dependent acid

L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

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de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

2011-05-01

Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

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M Sofiabadi

2012-05-01

Full Text Available

Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.

Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 

Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

Conclusion: This study showed

Cell surface binding and uptake of arginine- and lysine-rich penetratin peptides in absence and presence of proteoglycans

KAUST Repository

Å mand, Helene L.; Rydberg, Hanna A.; Fornander, Louise H.; Lincoln, Per; Nordé n, Bengt; Esbjö rner, Elin K.

2012-01-01

Cell surface proteoglycans (PGs) appear to promote uptake of arginine-rich cell-penetrating peptides (CPPs), but their exact functions are unclear. To address if there is specificity in the interactions of arginines and PGs leading to improved

[Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris].

Science.gov (United States)

Sozykin, A V; Noeva, E A; Balakhonova, T V; Pogorelova, O A; Men'shikov, M Iu

2000-01-01

Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

Acetylglutamate synthase in Neurospora crassa: characterization, localization, and genetic behavior of a regulatory enzyme of arginine biosynthesis

International Nuclear Information System (INIS)

Jacobson, J.A.

1988-01-01

This study describes the characterization and localization of the first enzyme of arginine biosynthesis in Neurospora crassa. A radioactive assay was developed to detect this enzyme whereby radioactive substrate and product molecules could be separated by ion-exchange chromatography. The enzyme was found to have a pH optimum of 9.0 and K/sub m/ values for glutamate and acetyl-CoA of approximately 4.7 and 0.45 mM, respectively. The enzyme was shown to be feedback inhibited by arginine. Half-maximal inhibition was observed at 0.13 mM arginine, a concentration which is similar to be in vivo cytosolic concentration of 0.2 mM. Arginine was found to act as a competitive inhibitor with respect to acetyl-CoA. Acetylglutamate synthase was localized to the mitochondrion. However, in contrast to the mitochondrial matrix location of the other ornithine biosynthetic enzymes, this enzyme was found to reside on the mitochondrial inner membrane

Effect of amino acids lysine and arginine on fracture healing in rabbits: A radiological and histomorphological analysis

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Sinha Shivam

2009-01-01

Full Text Available Background: Amino acids like arginine and lysine have been suggested to hasten the process of fracture healing by improving the local blood supply, supplementing growth factors, and improving collagen synthesis. We studied the role of lysine and arginine in the fracture repair process with regard to the rate of healing, probable mechanisms involved in the process, and mutual synergism between these agents. Materials and Methods: In an experimental study, 40 rabbits were subjected to ulnar osteotomy. They were distributed in control (14 and test groups (26. Twenty-six animals in the test group were fed with a diet rich in lysine and arginine. Both the groups were followed radiologically and histologically till union. Results: There was better healing of osteotomy in terms of better vascularization, callus formation, and mineralization in the test group. The time of healing in the test group was reduced by a period of 2 weeks. Conclusion: We conclude that amino acids like arginine and lysine may hasten fracture healing.

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

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Ramesh Chennupati

Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

Asymmetric Dimethyl Arginine in Hypothyroid Patients

International Nuclear Information System (INIS)

Abdel-Messeih, P.L.

2012-01-01

Thyroid diseases may lead to endothelial dysfunction, however, the mechanism underlying the endothelial dysfunction in thyroid disease is still not clear. Asymmetric dimethyl arginine (ADMA), a novel inhibitor of endothelial nitric oxide synthetase (eNOS), was reported to inhibit nitric oxide (NO) synthesis from L-arginine. The present study was carried out to investigate ADMA levels together with effects of dislipidemia in sub-clinical and overt hypothyroid females. There were significant increase in the levels of total cholesterol, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), thyroid stimulating hormone (TSH) and ADMA in hypothyroid females as compared to controls while the levels of NO and free T 4 were significantly decreased than controls. Sub-clinical hypothyroid females had significant high TSH, LDL-c and non-significantly high ADMA levels and total cholesterol as compared to controls while they had significant decrease in NO, HDL-c and non-significant decrease in free T 4 as compared to controls. There were significant negative correlations between NO and both ADMA (r 2 = 0.84) and free T 4 (r 2 = 0.95) in overt hypothyroid group while significant positive correlation (r 2 = 0.85) was detected between TSH and HDL-c in the same group. These results are highly suggestive that the decrease of nitric oxide secondary to accumulation of ADMA represent an important pathogenic factor together with dyslipidemia in endothelial dysfunction and increased cardiovascular risk especially in hypothyroid females

Asymmetric Dimethyl Arginine in Hypothyroid Patients

Energy Technology Data Exchange (ETDEWEB)

Abdel-Messeih, P. L. [Health Radiation Research Department, National Centre for Radiation Research and Technology, Cairo (Egypt)

2012-07-01

Thyroid diseases may lead to endothelial dysfunction, however, the mechanism underlying the endothelial dysfunction in thyroid disease is still not clear. Asymmetric dimethyl arginine (ADMA), a novel inhibitor of endothelial nitric oxide synthetase (eNOS), was reported to inhibit nitric oxide (NO) synthesis from L-arginine. The present study was carried out to investigate ADMA levels together with effects of dislipidemia in sub-clinical and overt hypothyroid females. There were significant increase in the levels of total cholesterol, low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), thyroid stimulating hormone (TSH) and ADMA in hypothyroid females as compared to controls while the levels of NO and free T{sub 4} were significantly decreased than controls. Sub-clinical hypothyroid females had significant high TSH, LDL-c and non-significantly high ADMA levels and total cholesterol as compared to controls while they had significant decrease in NO, HDL-c and non-significant decrease in free T{sub 4} as compared to controls. There were significant negative correlations between NO and both ADMA (r{sup 2} = 0.84) and free T{sub 4} (r{sup 2} = 0.95) in overt hypothyroid group while significant positive correlation (r{sup 2} = 0.85) was detected between TSH and HDL-c in the same group. These results are highly suggestive that the decrease of nitric oxide secondary to accumulation of ADMA represent an important pathogenic factor together with dyslipidemia in endothelial dysfunction and increased cardiovascular risk especially in hypothyroid females.

Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke

DEFF Research Database (Denmark)

Molnar, Tihamer; Pusch, Gabriella; Nagy, Lajos

2016-01-01

BACKGROUND: Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive...... and independent associations to outcome. METHODS: Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed...... as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. RESULTS: Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most...

EG-01EPIGENETIC INACTIVATION OF ARGININE BIOSYNTHESIS PATHWAY IN PAEDIATRIC HIGH GRADE GLIOMA

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Channathodiyil, Prasanna; Kardooni, Hoda; Khozoie, Combiz; Nelofer, Syed; Darling, John; Morris, Mark; Warr, Tracy

2014-01-01

Aberrant cellular metabolism contributes significantly to the growth and proliferation of several tumour types. Identification of genes that control critical metabolic pathways is a major factor in the development of novel therapies that target metabolic defects in tumour cells. Our aim is to identify such genes in paediatric high grade glioma that are altered due to promoter hyper-methylation of cytosine residues in CpG dinucleotides. Genome wide DNA methylation profiling using Illumina infinium methylation 450K bead chip array was performed on 18 well-characterised short term cultures derived from paediatric high grade astrocytoma including 3 from diffuse intrinsic pontine glioma. Data analyses were based on beta scores of probes for each gene as measures of intensities of methylation. Genes were selected with beta scores of tumour > =0.70 and that of normal human astrocytes < =0.30. We identified that two vital genes involved in the regulation of arginine biosynthetic pathway, argininosuccinate synthetase 1(ASS1) and argininosuccinate lyase (ASL) were methylated in 9/18 (50%) cases. Hyper methylation was confirmed by methylation-specific PCR and up-regulation of gene expression following treatment with 2 µM 5-aza-2'-deoxyctidine. Down-regulation of ASS1 in hyper methylated samples was confirmed by Western blot analysis. Our findings report epigenetic deregulation of ASS1 and ASL in a subset of paediatric high grade glioma. The enzymes encoded by these genes are essential elements of urea cycle that function together in the de novo synthesis of arginine from citrulline. Tumour cells with deficient ASS1/ASL depend on external sources of arginine for survival and have been reported to be sensitive to autophagic cell death induced by arginine starvation. Therefore, further investigation may render the possibility of arginine-deprivation therapy in such sub type of paediatric high grade glioma. This therapeutic approach is of interest as tumour cells with abnormal

Mimicking of Arginine by Functionalized N(ω)-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples.

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Keller, Max; Kuhn, Kilian K; Einsiedel, Jürgen; Hübner, Harald; Biselli, Sabrina; Mollereau, Catherine; Wifling, David; Svobodová, Jaroslava; Bernhardt, Günther; Cabrele, Chiara; Vanderheyden, Patrick M L; Gmeiner, Peter; Buschauer, Armin

2016-03-10

Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N-terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of-concept study. The N(ω)-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.

In vitro study of the effect of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate on acid-softened enamel.

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Rege, Aarti; Heu, Rod; Stranick, Michael; Sullivan, Richard J

2014-01-01

To investigate the possible mode of action of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin Technology), and sodium monofluorophosphate in delivering the benefits of preventing acid erosion and rehardening acid-softened enamel. The surfaces of acid-softened bovine enamel specimens were evaluated after application of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate in vitro. Scanning Electron Microscopy (SEM), Electronic Spectrometry for Chemical Analysis (ESCA), and Secondary Ion Mass Spectrometry (SIMS) were used to characterize the enamel surfaces. Exposure of pristine enamel surfaces to citric acid resulted in clear roughening of the surface. Multiple applications of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to the surface of the enamel resulted in the disappearance of the microscopic voids observed by SEM as a function of treatment applications. The ESCA analysis demonstrated that both the nitrogen and carbonate levels increased as the number of treatments increased, which provides evidence that arginine and calcium carbonate were bound to the surface. Observance of arginine's signature mass fragmentation pattern by SIMS analysis confirmed the identity of arginine on the enamel surface. A series of in vitro experiments has demonstrated a possible mode of action by which a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate delivers the benefits of preventing acid erosion and rehardening acid-softened enamel. The combination of arginine and calcium carbonate adheres to the enamel surface and helps to fill the microscopic gaps created by acid, which in turn helps repair the enamel and provides a protective coating against future acid attacks.

Asymmetric Arginine dimethylation of Epstein-Barr virus nuclear antigen 2 promotes DNA targeting

International Nuclear Information System (INIS)

Gross, Henrik; Barth, Stephanie; Palermo, Richard D.; Mamiani, Alfredo; Hennard, Christine; Zimber-Strobl, Ursula; West, Michelle J.; Kremmer, Elisabeth; Graesser, Friedrich A.

2010-01-01

The Epstein-Barr virus (EBV) growth-transforms B-lymphocytes. The virus-encoded nuclear antigen 2 (EBNA2) is essential for transformation and activates gene expression by association with DNA-bound transcription factors such as RBPJκ (CSL/CBF1). We have previously shown that EBNA2 contains symmetrically dimethylated Arginine (sDMA) residues. Deletion of the RG-repeat results in a reduced ability of the virus to immortalise B-cells. We now show that the RG repeat also contains asymmetrically dimethylated Arginines (aDMA) but neither non-methylated (NMA) Arginines nor citrulline residues. We demonstrate that only aDMA-containing EBNA2 is found in a complex with DNA-bound RBPJκ in vitro and preferentially associates with the EBNA2-responsive EBV C, LMP1 and LMP2A promoters in vivo. Inhibition of methylation in EBV-infected cells results in reduced expression of the EBNA2-regulated viral gene LMP1, providing additional evidence that methylation is a prerequisite for DNA-binding by EBNA2 via association with the transcription factor RBPJκ.

Inhibition of Clostridium difficile toxin A and B by 1,2-cyclohexanedione modification of an arginine residue.

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Balfanz, J; Rautenberg, P

1989-12-29

Toxin A (enterotoxin) and toxin B (cytotoxin) of Clostridium difficile were both inactivated by the arginine specific reagent 1,2-cyclohexanedione. Molecular stability during the inactivation process was demonstrated by SDS-PAGE analysis showing the same migration rates for modified and unmodified forms of the 230 kDa toxin A and of the 250 kDa toxin B. Cytotoxicity of both toxins as well as mouse lethality of the enterotoxin were drastically decreased as a result of the arginine modification. The reaction followed pseudo-first-order kinetics. Analysis of the data suggested that modification of a single arginine residue was sufficient to abolish the activity of both toxins.

EFFECTS OF ARGININE AND VITAMIN E SUPPLEMENTED DIETS ON THE IMMUNOLOGICAL RESPONSE OF BROILERS CHICKENS

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David Jesús Chan Diaz

2012-08-01

Full Text Available In order to evaluate the effect of arginine and vitamin E supplementation in broiler chicken diets on the immune response during post-vaccine stress, a trial was conducted with 700 chicks (1 day-old which were distributed into 28 floor-pens and fed one of four dietary treatments (with 7 replicates randomly assigned: T1 = control diet (1.31 % of arginine and 10 IU of vitamin E/kg of feed; T2 = T1 + 0.3 % of arginine; T3 = T1 + 70 IU of vitamin E; T4 = T1 + 0.3 % of arginine + 70 IU of vitamin E. At 12 days of age, all birds were vaccinated against Newcastle disease virus (ND, infectious bronchitis, avian influenza (AI and fowl pox. The traits evaluated were: post-vaccine reaction at days 14, 16, 18, 21 and 23; antibody titers against ND and AI, and relative lymphoid organs weight at days 11, 19 and 26; and the performance were recorded weekly. Chickens fed T2, T4 (at day 16, and T3 (at day 21 had lesser (p≤0.05 post-vaccine reaction than birds fed T1. The antibody titers against ND (at day 11 was higher (p≤0.05 in chickens fed T4 (3.1, T3 (2.7 and T2 (2.7 compared to T1 (1.6; meanwhile, for AI titers no differences were found. There were no differences, neither for immune organs weight, nor for performance. In conclusion, arginine and vitamin E supplementation in broiler chicken diets reduced the post-vaccine stress and improved the immune response without affecting the performance.

The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

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Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

2012-11-01

Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Arginine Coordination in Enzymatic Phosphoryl Transfer: Evaluation of the Effect of Arg166 Mutations in Escherichia Coli Alkaline Phosphatase

International Nuclear Information System (INIS)

O'Brien, P.J.; Lassila, J.K.; Fenn, T.D.; Zalatan, J.G.; Herschlag, D.

2008-01-01

Arginine residues are commonly found in the active sites of enzymes catalyzing phosphoryl transfer reactions. Numerous site-directed mutagenesis experiments establish the importance of these residues for efficient catalysis, but their role in catalysis is not clear. To examine the role of arginine residues in the phosphoryl transfer reaction, we have measured the consequences of mutations to arginine 166 in Escherichia coli alkaline phosphatase on hydrolysis of ethyl phosphate, on individual reaction steps in the hydrolysis of the covalent enzyme-phosphoryl intermediate, and on thio substitution effects. The results show that the role of the arginine side chain extends beyond its positive charge, as the Arg166Lys mutant is as compromised in activity as Arg166Ser. Through measurement of individual reaction steps, we construct a free energy profile for the hydrolysis of the enzyme-phosphate intermediate. This analysis indicates that the arginine side chain strengthens binding by ∼3 kcal/mol and provides an additional 1-2 kcal/mol stabilization of the chemical transition state. A 2.1 (angstrom) X-ray diffraction structure of Arg166Ser AP is presented, which shows little difference in enzyme structure compared to the wild-type enzyme but shows a significant reorientation of the bound phosphate. Altogether, these results support a model in which the arginine contributes to catalysis through binding interactions and through additional transition state stabilization that may arise from complementarity of the guanidinum group to the geometry of the trigonal bipyramidal transition state

Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

Science.gov (United States)

Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

2013-07-01

The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

Arginine Deprivation Inhibits the Warburg Effect and Upregulates Glutamine Anaplerosis and Serine Biosynthesis in ASS1-Deficient Cancers

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Jeff Charles Kremer

2017-01-01

Full Text Available Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1 is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect. The reduction of glycolysis in cells otherwise dependent on aerobic glycolysis is correlated with reduced PKM2 expression and phosphorylation and upregulation of PHGDH. Concurrent arginine deprivation and glutaminase inhibition was found to be synthetic lethal across a spectrum of ASS1-deficient tumor cell lines and is sufficient to cause in vivo tumor regression in mice. These results identify two synthetic lethal therapeutic strategies exploiting metabolic vulnerabilities of ASS1-negative cancers.

The Metabolic Conversion of Arginine in the Rumen Wall and its Importance in Ruminant Nitrogen Metabolism

Energy Technology Data Exchange (ETDEWEB)

Harmeyer, J.; Kurelec, B.; Hill, H. [Department of Physiology, School of Veterinary Medicine, Hanover, Federal Republic of Germany (Germany)

1968-07-01

The functions of arginase and urease of the rumen wall were investigated in vitro and in vivo. Surviving ruminal mucosae of cattle were incubated for four hours. {sup 14}C-arginine-HCl, uniformly labelled, was added to the serosal side at a concentration of 10 pmol/mi. About 25% of the added arginine was used during the incubation by the ruminal tissue. In comparison with controls an increased amount of {sup 14}C-omithine, urea, and ammonia were formed in the mucosa and appeared on both sides. The increase was due to arginase and urease functions. It was estimated that about 50% of the urea formed by arginine breakdown were present at the mucosa side, mainly in the form of ammonia. Of the omithine simultaneously formed, 85% remained on the serosa side. Remarkable individual variations of omithine and urea formation were found from animal to animal. The in-vivo experiments were performed using goats with catheters placed in the right ruminal artery and vein. We injected 90 {mu}Ci of {sup 14}C-arginine into the ruminal artery. When 80 g of soluble starch were added to the rumen the activity and concentration of ornithine increased in the ruminal venous blood showing an arterial-venous difference. The radioactivity of urea in blood taken from the ruminal vein and the carotid artery did not show any difference. When starch was omitted from the rumen a comparable difference of omithine concentration was not found. It is assumed that the enzymes arginase and urease of the rumen wall are involved in nitrogen recycling processes. Blood arginine may be hydrolysed in the rumen wall forming urea and ornithine. Urea formed by arginine breakdown may be split to CO{sub 2} and ammonia. The experiments produced evidence that the ammonia formed preferably enters the rumen content. The nitrogen transfer through the rumen wall may be affected by varying activities of arginase. (author)

Gas-phase salt bridge interactions between glutamic acid and arginine

NARCIS (Netherlands)

Jaeqx, S.; Oomens, J.; Rijs, A.M.

2013-01-01

The gas-phase side chain-side chain (SC-SC) interaction and possible proton transfer between glutamic acid (Glu) and arginine (Arg) residues are studied under low-temperature conditions in an overall neutral peptide. Conformation-specific IR spectra, obtained with the free electron laser FELIX, in

Caries-free subjects have high levels of urease and arginine deiminase activity

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Evelyn REYES

2014-06-01

Full Text Available Objectives: This study investigated the relationship between urease and arginine deiminase system (ADS activities and dental caries through a cross-sectional study. Material and Methods: Urease and ADS activities were measured in saliva and plaque samples from 10 caries-free subjects and 13 caries-active. Urease activity was obtained from the ammonia produced by incubation of plaque and saliva samples in urea. ADS activity was obtained from the ammonia generated by the arginine-HCl and Tris-maleate buffer. Specific activity was defined as micromoles of ammonia per minute per milligram of protein. Shapiro-Wilk statistical test was used to analyze the distribution of the data, and Mann-Whitney test was used to determine the significance of the data. Results: The specific urease activity in saliva and plaque was significantly higher in individuals with low DMFT scores. ADS activity in saliva (6.050 vs 1.350, p=0.0154 and plaque (8.830 vs 1.210, p=0.025 was also higher in individuals with low DMFT scores. Conclusions: Caries-free subjects had a higher ammonia generation activity by urease and arginine deiminase system for both saliva and plaque samples than low caries-active subjects. High levels of alkali production in oral environment were related to caries-free subjects.

Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung.

Science.gov (United States)

Grasemann, C; Herrmann, R; Starschinova, J; Gertsen, M; Palmert, M R; Grasemann, H

2017-02-20

Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

Short-term arginine deprivation results in large-scale modulation of hepatic gene expression in both normal and tumor cells: microarray bioinformatic analysis

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Sabo Edmond

2006-09-01

Full Text Available Abstract Background We have reported arginine-sensitive regulation of LAT1 amino acid transporter (SLC 7A5 in normal rodent hepatic cells with loss of arginine sensitivity and high level constitutive expression in tumor cells. We hypothesized that liver cell gene expression is highly sensitive to alterations in the amino acid microenvironment and that tumor cells may differ substantially in gene sets sensitive to amino acid availability. To assess the potential number and classes of hepatic genes sensitive to arginine availability at the RNA level and compare these between normal and tumor cells, we used an Affymetrix microarray approach, a paired in vitro model of normal rat hepatic cells and a tumorigenic derivative with triplicate independent replicates. Cells were exposed to arginine-deficient or control conditions for 18 hours in medium formulated to maintain differentiated function. Results Initial two-way analysis with a p-value of 0.05 identified 1419 genes in normal cells versus 2175 in tumor cells whose expression was altered in arginine-deficient conditions relative to controls, representing 9–14% of the rat genome. More stringent bioinformatic analysis with 9-way comparisons and a minimum of 2-fold variation narrowed this set to 56 arginine-responsive genes in normal liver cells and 162 in tumor cells. Approximately half the arginine-responsive genes in normal cells overlap with those in tumor cells. Of these, the majority was increased in expression and included multiple growth, survival, and stress-related genes. GADD45, TA1/LAT1, and caspases 11 and 12 were among this group. Previously known amino acid regulated genes were among the pool in both cell types. Available cDNA probes allowed independent validation of microarray data for multiple genes. Among genes downregulated under arginine-deficient conditions were multiple genes involved in cholesterol and fatty acid metabolism. Expression of low-density lipoprotein receptor was

Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

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Wells, James W; Evans, Christopher H; Scott, Milcah C; Rütgen, Barbara C; O'Brien, Timothy D; Modiano, Jaime F; Cvetkovic, Goran; Tepic, Slobodan

2013-01-01

Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

Development of Isocratic RP-HPLC Method for Separation and Quantification of L-Citrulline and L-Arginine in Watermelons

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Rasdin Ridwan

2018-01-01

Full Text Available Watermelons (Citrullus lanatus are known to have sufficient amino acid content. In this study, watermelons grown and consumed in Malaysia were investigated for their amino acid content, L-citrulline and L-arginine, by the isocratic RP-HPLC method. Flesh and rind watermelons were juiced, and freeze-dried samples were used for separation and quantification of L-citrulline and L-arginine. Three different mobile phases, 0.7% H3P04, 0.1% H3P04, and 0.7% H3P04 : ACN (90 : 10, were tested on two different columns using Zorbax Eclipse XDB-C18 and Gemini C18 with a flow rate of 0.5 mL/min and a detection wavelength at 195 nm. Efficient separation with reproducible resolution of L-citrulline and L-arginine was achieved using 0.1% H3P04 on the Gemini C18 column. The method was validated and good linearity of L-citrulline and L-arginine was obtained with R2 = 0.9956, y=0.1664x+2.4142 and R2=0.9912, y=0.4100x+3.4850, respectively. L-citrulline content showed the highest concentration in red watermelon of flesh and rind juice extract (43.81 mg/g and 45.02 mg/g, whereas L-arginine concentration was lower than L-citrulline, ranging from 3.39 to 11.14 mg/g. The isocratic RP-HPLC method with 0.1% H3P04 on the Gemini C18 column proved to be efficient for separation and quantification of L-citrulline and L-arginine in watermelons.

Randomized clinical trial of arginine-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing gastric cancer surgery.

Science.gov (United States)

Zhao, Hongyan; Zhao, Hongying; Wang, Yu; Jing, Huang; Ding, Qian; Xue, Jun

2013-09-01

Significant malnutrition exists in a high percentage of patients with gastric cancer. It is, therefore, crucial to establish an effective means to provide nutrition for these patients. This prospective, randomized, double-blinded clinical trial aims to assess the long-term survival of arginine-supplementation enteral nutrition versus standard enteral nutrition in malnourished patients with gastric cancer. The control group (36 cases) received postoperative standard enteral nutrition. Meanwhile, the arginine-supplementation group (37 cases) adopted the same nutrition product but enriched with arginine (9.0 g/L). The primary study objective was overall survival (OS). Secondary endpoints were progression-free survival (PFS); serum parameters including total protein, albumin, proalbumin, and transferrin obtained on preoperative day 1, postoperative day 2, and day 12; CD4(+) and CD8(+) T cells, natural killer (NK) cells, immunoglobulin M (IgM), and immunoglobulin G (IgG) obtained on preoperative day 1 and postoperative day 7. No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better OS (P = 0.03, 41 vs. 30.5 months) and better PFS (P = 0.02, 18 vs. 11.5 months). On postoperative day 7, CD4(+) T cells, NK cells, IgM and IgG levels of the arginine-supplemented group increased prominently and were significantly higher than those of the control group and those on preoperative day 1. There is no significant difference in the serum total protein, albumin, proalbumin, and transferrin levels between the two arms. Arginine-supplemented enteral nutrition significantly improves long-term survival and restores immunity in malnourished gastric cancer.

The Effect of L-arginine Supplementation on Blood Pressure in Patients with Type 2 Diabetes: A Double-Blind Randomized Clinical Trial

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Sara Asadi

2016-10-01

Full Text Available Background: The prevalence of hypertension in patients with type 2 diabetes (T2D is approximately twice as much as healthy people. This study was designed to determine the effect of L-arginine supplementation on blood pressure in patients with T2D. Methods: In a double-blind randomized clinical trial, 75 T2D were randomly divided into three groups (3 g/d and 6g/d of L-arginine and placebo for 3 months. Height, weight, waist circumference, dietary intake, and blood pressure (BP were measured before and after intervention. Results: In patients who received 3g/d L-arginine, no significant difference was observed between BP before and after the intervention, however, subgroup analysis among patients with high BP showed significant reduction in systolic (P = 0.036 and diastolic BP (P = 0.027 after L-arginine supplementation. After 3 months of intervention, systolic and diastolic BP were significantly different compared to the baseline values and also with placebo value in patients receiving 6g/d of L-arginine (P < 0.05. Conclusions: The daily intake of 6g of L-arginine for 3 months in T2D may improve BP. Taking 3g/d of this supplement may help to improve BP only in patients with hypertension.

Effect of rare-earth dopants on the growth and structural, optical, electrical and mechanical properties of L-arginine phosphate single crystals

International Nuclear Information System (INIS)

Arjunan, S.; Bhaskaran, A.; Kumar, R. Mohan; Mohan, R.; Jayavel, R.

2010-01-01

Research highlights: → Thorium, Lanthanum and Cerium rare-earth ions were doped with L-arginine phosphate material and the crystals were grown by slow evaporation technique. → The transparency of the rare-earth doped LAP crystals has enhanced compared to pure LAP. → The powder SHG measurements revealed that the SHG output of rare-earth doped LAP crystals increases considerably compared to that of LAP. → Vicker's hardness number of as-grown crystal of LAP is higher than that of rare-earth doped LAP crystals. - Abstract: Effect of Thorium, Lanthanum and Cerium rare-earth ions on the growth and properties of L-arginine phosphate single crystals has been reported. The incorporation of rare-earth dopants into the L-arginine phosphate crystals is confirmed by Inductively Coupled Plasma-Mass Spectroscopy analysis. The unit cell parameters for pure and rare-earth doped L-arginine phosphate crystals have been estimated by powder X-ray diffraction studies. UV-visible studies revealed the transmittance percentage and cut-off wavelengths of the grown crystals. Powder second harmonic generation measurement has been carried out for pure and doped L-arginine phosphate crystals. The dielectric behavior of the grown crystals was analyzed for different frequencies at room temperature. The mechanical properties have been determined for pure and the doped L-arginine phosphate crystals.

A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.

Science.gov (United States)

Kudo, Shinpei; Nagasaki, Yukio

2015-11-10

In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

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Parveen Sharma

2010-07-01

Full Text Available Phospholamban (PLN is an effective inhibitor of the sarco(endoplasmic reticulum Ca(2+-ATPase, which transports Ca(2+ into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation.Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins.We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

DEFF Research Database (Denmark)

Nossent, Anne Yaël; Robben, J H; Deen, P M T

2010-01-01

SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice

NARCIS (Netherlands)

Luiking, Yvette C.; Hallemeesch, Marcella M.; Lamers, Wouter H.; Deutz, Nicolaas E. P.

2005-01-01

Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino

Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma

NARCIS (Netherlands)

Maarsingh, Ham; Leusink, John; Zaagsma, Johan; Meurs, Herman

2006-01-01

Nitric oxide synthase (NOS) converts L-arginine into nitric oxide (NO) and L-Citrulline. In NO-producing cells, L-citrulline can be recycled to L-arginine in a two-step reaction involving argininosuccinate synthase (ASS) and -lyase (ASL). In guinea pig trachea, L-arginine is a limiting factor in

The Microbiome, Intestinal Function, and Arginine Metabolism of Healthy Indian Women Are Different from Those of American and Jamaican Women.

Science.gov (United States)

Kao, Christina C; Cope, Julia L; Hsu, Jean W; Dwarkanath, Pratibha; Karnes, Jeffrey M; Luna, Ruth A; Hollister, Emily B; Thame, Minerva M; Kurpad, Anura V; Jahoor, Farook

2016-03-09

Indian women have slower arginine flux during pregnancy compared with American and Jamaican women. Arginine is a semi-essential amino acid that becomes essential during periods of rapid lean tissue deposition. It is synthesized only from citrulline, a nondietary amino acid produced mainly in the gut. The gut is therefore a key site of arginine and citrulline metabolism, and gut microbiota may affect their metabolism. The objective of this study was to identify differences in the gut microbiota of nonpregnant American, Indian, and Jamaican women and characterize the relations between the gut microbiota, gut function, and citrulline and arginine metabolism. Thirty healthy American, Indian, and Jamaican women (n = 10/group), aged 28.3 ± 0.8 y, were infused intravenously with [guanidino- 15 N 2 ]arginine, [5,5- 2 H 2 ]citrulline, and [ 15 N 2 ]ornithine and given oral [U- 13 C 6 ]arginine in the fasting and postprandial states. Fecal bacterial communities were characterized by 16S rRNA gene sequencing. In the fasting state, Indian women had lower citrulline flux than did American and Jamaican women [7.0 ± 0.4 compared with 9.1 ± 0.4 and 8.9 ± 0.2 μmol ⋅ kg fat-free mass (FFM) -1  ⋅ h -1 , P = 0.01] and greater enteral arginine conversion to ornithine than did American women (1.4 ± 0.11 compared with 1.0 ± 0.08 μmol ⋅ kg FFM -1  ⋅ h -1 , P = 0.04). They also had lower mannitol excretion than American and Jamaican women (154 ± 37.1 compared with 372 ± 51.8 and 410 ± 39.6 mg/6 h, P Indian women had increased mean relative abundances of Prevotella (42%) compared to American and Jamaican women (7% and Indian women. © 2016 American Society for Nutrition.

Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

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James W Wells

Full Text Available Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

An Arginine Finger Regulates the Sequential Action of Asymmetrical Hexameric ATPase in the Double-Stranded DNA Translocation Motor.

Science.gov (United States)

Zhao, Zhengyi; De-Donatis, Gian Marco; Schwartz, Chad; Fang, Huaming; Li, Jingyuan; Guo, Peixuan

2016-10-01

Biological motors are ubiquitous in living systems. Currently, how the motor components coordinate the unidirectional motion is elusive in most cases. Here, we report that the sequential action of the ATPase ring in the DNA packaging motor of bacteriophage ϕ29 is regulated by an arginine finger that extends from one ATPase subunit to the adjacent unit to promote noncovalent dimer formation. Mutation of the arginine finger resulted in the interruption of ATPase oligomerization, ATP binding/hydrolysis, and DNA translocation. Dimer formation reappeared when arginine mutants were mixed with other ATPase subunits that can offer the arginine to promote their interaction. Ultracentrifugation and virion assembly assays indicated that the ATPase was presenting as monomers and dimer mixtures. The isolated dimer alone was inactive in DNA translocation, but the addition of monomer could restore the activity, suggesting that the hexameric ATPase ring contained both dimer and monomers. Moreover, ATP binding or hydrolysis resulted in conformation and entropy changes of the ATPase with high or low DNA affinity. Taking these observations together, we concluded that the arginine finger regulates sequential action of the motor ATPase subunit by promoting the formation of the dimer inside the hexamer. The finding of asymmetrical hexameric organization is supported by structural evidence of many other ATPase systems showing the presence of one noncovalent dimer and four monomer subunits. All of these provide clues for why the asymmetrical hexameric ATPase gp16 of ϕ29 was previously reported as a pentameric configuration by cryo-electron microscopy (cryo-EM) since the contact by the arginine finger renders two adjacent ATPase subunits closer than other subunits. Thus, the asymmetrical hexamer would appear as a pentamer by cryo-EM, a technology that acquires the average of many images. Copyright © 2016 Zhao et al.

Comparison of the effect of topical versus systemic L-arginine on wound healing in acute incisional diabetic rat model

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Alireza Zandifar

2015-01-01

Full Text Available Background: Diabetes is associated with endothelial dysfunction and impaired wound healing. The amino acid L-arginine is the only substrate for nitric oxide (NO synthesis. The purpose of this study was to compare the topical versus systemic L-arginine treatment on total nitrite (NO x and vascular endothelial growth factor (VEGF concentrations in wound fluid and rate of wound healing in an acute incisional diabetic wound model. Materials and Methods: A total of 56 Sprague-Dawley rats were used of which 32 were rendered diabetic. Animals underwent a dorsal skin incision. Dm-sys-arg group (N = 8, diabetic and Norm-sys-arg group (N = 8, normoglycemic were gavaged with L-arginine. Dm-sys-control group (N = 8, diabetic and Norm-sys-control group (N = 8, normoglycemic were gavaged with water. Dm-top-arg group (N = 8, diabetic and norm-top-arg group (N = 8, normoglycemic received topical L-arginine gel. Dm-top-control group (N = 8, diabetic received gel vehicle. On the day 5 the amount of NO x in wound fluid was measured by Griess reaction. VEGF/total protein in wound fluids was also measured on day 5 using enzyme-linked immunosorbent assay. All wound tissue specimens were fixed and stained to be evaluated for rate of healing. Data were analyzed using SPSS software (version 18.0, Chicago, IL, USA through One-way analysis of variance test and Tukey′s post-hoc. Results: In dm-sys-arg group, the level of NO x on day 5 was significantly more than dm-top-arg group (P < 0.05. VEGF content in L-arginine treated groups were significantly more than controls (P < 0.05. Rate of diabetic wound healing in dm-sys-arg group was significantly more than dm-top-arg group. Conclusion: Systemic L-arginine is more efficient than topical L-arginine in wound healing. This process is mediated at least in part, by increasing VEGF and NO in the wound fluid.

Effect of rare-earth dopants on the growth and structural, optical, electrical and mechanical properties of L-arginine phosphate single crystals

Energy Technology Data Exchange (ETDEWEB)

Arjunan, S., E-mail: arjunan_hce@yahoo.co.i [Department of Physics, Sri Ramachandra University, Porur, Chennai (India); Bhaskaran, A. [Department of Physics, Dr. Ambedkar Government College, Chennai (India); Kumar, R. Mohan; Mohan, R. [Department of Physics, Presidency College, Chennai (India); Jayavel, R. [Crystal Growth Centre, Anna University, Chennai (India)

2010-09-17

Research highlights: {yields} Thorium, Lanthanum and Cerium rare-earth ions were doped with L-arginine phosphate material and the crystals were grown by slow evaporation technique. {yields} The transparency of the rare-earth doped LAP crystals has enhanced compared to pure LAP. {yields} The powder SHG measurements revealed that the SHG output of rare-earth doped LAP crystals increases considerably compared to that of LAP. {yields} Vicker's hardness number of as-grown crystal of LAP is higher than that of rare-earth doped LAP crystals. - Abstract: Effect of Thorium, Lanthanum and Cerium rare-earth ions on the growth and properties of L-arginine phosphate single crystals has been reported. The incorporation of rare-earth dopants into the L-arginine phosphate crystals is confirmed by Inductively Coupled Plasma-Mass Spectroscopy analysis. The unit cell parameters for pure and rare-earth doped L-arginine phosphate crystals have been estimated by powder X-ray diffraction studies. UV-visible studies revealed the transmittance percentage and cut-off wavelengths of the grown crystals. Powder second harmonic generation measurement has been carried out for pure and doped L-arginine phosphate crystals. The dielectric behavior of the grown crystals was analyzed for different frequencies at room temperature. The mechanical properties have been determined for pure and the doped L-arginine phosphate crystals.

L-arginine and L-NMMA for Assessing Cerebral Endothelial Dysfunction in Ischemic Cerebrovascular Disease: A Systematic Review

DEFF Research Database (Denmark)

Karlsson, William Kristian; Sørensen, Caspar Godthaab; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and NG -monomethyl-l-arginine (l......-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible...... cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease....

L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

NARCIS (Netherlands)

Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

Binding of the human "electron transferring flavoprotein" (ETF) to the medium chain acyl-CoA dehydrogenase (MCAD) involves an arginine and histidine residue.

Science.gov (United States)

Parker, Antony R

2003-10-01

The interaction between the "electron transferring flavoprotein" (ETF) and medium chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron transfer, crucial for the beta-oxidation of fatty acids. The exact biochemical determinants for ETF binding to MCAD are unknown. Here we show that binding of human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate (DEPC) and reversed by incubation with free arginine and hydroxylamine respectively. Spectral analyses of native ETF vs modified ETF suggested that flavin binding was not affected and that the loss of ETF activity with MCAD involved modification of one ETF arginine residue and one ETF histidine residue respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both 2,3-butanedione and DEPC indicating that the arginine and histidine residues are present in or around the MCAD binding site. Comparison of exposed arginine and histidine residues among different ETF species, however, indicates that arginine residues are highly conserved but that histidine residues are not. These results lead us to conclude that this single arginine residue is essential for the binding of ETF to MCAD, but that the single histidine residue, although involved, is not.

Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects

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Beverly Giam

2016-06-01

Full Text Available Obesity related hypertension is a major risk factor for resistant hypertension. We do not completely understand the mechanism(s underlying the development of obesity related hypertension which hinders the development of novel treatment strategies for this condition. Data from experimental studies and small clinical trials indicate that transport of l-arginine, the substrate for nitric oxide (NO, and subsequent NO production are reduced in obesity induced hypertension. Reduced NO bioavailability can induce hypertension via multiple mechanisms. Mirmiran et al. recently analyzed data from a large population study and found that the association between dietary l-arginine and serum nitrate and nitrite was weakened in obese hypertensive subjects compared to obese normotensives. These data suggest that l-arginine dependent NO production is impaired in the former group compared to the latter which may represent a novel mechanism contributing to hypertension in the setting of obesity.

Rmt1 catalyzes zinc-finger independent arginine methylation of ribosomal protein Rps2 in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Lipson, Rebecca S.; Webb, Kristofor J.; Clarke, Steven G.

2010-01-01

Rps2/rpS2 is a well conserved protein of the eukaryotic ribosomal small subunit. Rps2 has previously been shown to contain asymmetric dimethylarginine residues, the addition of which is catalyzed by zinc-finger-containing arginine methyltransferase 3 (Rmt3) in the fission yeast Schizosaccharomyces pombe and protein arginine methyltransferase 3 (PRMT3) in mammalian cells. Here, we demonstrate that despite the lack of a zinc-finger-containing homolog of Rmt3/PRMT3 in the budding yeast Saccharomyces cerevisiae, Rps2 is partially modified to generate asymmetric dimethylarginine and monomethylarginine residues. We find that this modification of Rps2 is dependent upon the major arginine methyltransferase 1 (Rmt1) in S. cerevisiae. These results are suggestive of a role for Rmt1 in modifying the function of Rps2 in a manner distinct from that occurring in S. pombe and mammalian cells.

Unveiling the Mechanism of Arginine Transport through AdiC with Molecular Dynamics Simulations: The Guiding Role of Aromatic Residues.

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Eva-Maria Krammer

Full Text Available Commensal and pathogenic enteric bacteria have developed several systems to adapt to proton leakage into the cytoplasm resulting from extreme acidic conditions. One such system involves arginine uptake followed by export of the decarboxylated product agmatine, carried out by the arginine/agmatine antiporter (AdiC, which thus works as a virtual proton pump. Here, using classical and targeted molecular dynamics, we investigated at the atomic level the mechanism of arginine transport through AdiC of E. coli. Overall, our MD simulation data clearly demonstrate that global rearrangements of several transmembrane segments are necessary but not sufficient for achieving transitions between structural states along the arginine translocation pathway. In particular, local structural changes, namely rotameric conversions of two aromatic residues, are needed to regulate access to both the outward- and inward-facing states. Our simulations have also enabled identification of a few residues, overwhelmingly aromatic, which are essential to guiding arginine in the course of its translocation. Most of them belong to gating elements whose coordinated motions contribute to the alternating access mechanism. Their conservation in all known E. coli acid resistance antiporters suggests that the transport mechanisms of these systems share common features. Last but not least, knowledge of the functional properties of AdiC can advance our understanding of the members of the amino acid-carbocation-polyamine superfamily, notably in eukaryotic cells.

Combinatorial Effects of Arginine and Fluoride on Oral Bacteria

OpenAIRE

Zheng, X.; Cheng, X.; Wang, L.; Qiu, W.; Wang, S.; Zhou, Y.; Li, M.; Li, Y.; Cheng, L.; Li, J.; Zhou, X.; Xu, X.

2015-01-01

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicati...

Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

DEFF Research Database (Denmark)

Knuhtsen, Astrid; Legrand, Baptiste; Van der Poorten, Olivier

2016-01-01

Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-pr...

Serum Stabilities of Short Tryptophan-and Arginine-Rich Antimicrobial Peptide Analogs

NARCIS (Netherlands)

Nguyen, L.T.; Chau, J.K.; Perry, N.A.; de Boer, L.; Zaat, S.A.J.; Vogel, H.J.

2010-01-01

Background: Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the "antimicrobial

Bi-enzyme L-arginine-selective amperometric biosensor based on ammonium-sensing polyaniline-modified electrode.

Science.gov (United States)

Stasyuk, Nataliya; Smutok, Oleh; Gayda, Galina; Vus, Bohdan; Koval'chuk, Yevgen; Gonchar, Mykhailo

2012-01-01

A novel L-arginine-selective amperometric bi-enzyme biosensor based on recombinant human arginase I isolated from the gene-engineered strain of methylotrophic yeast Hansenula polymorpha and commercial urease is described. The biosensing layer was placed onto a polyaniline-Nafion composite platinum electrode and covered with a calcium alginate gel. The developed sensor revealed a good selectivity to L-arginine. The sensitivity of the biosensor was 110 ± 1.3 nA/(mM mm(2)) with the apparent Michaelis-Menten constant (K(M)(app)) derived from an L-arginine (L-Arg) calibration curve of 1.27 ± 0.29 mM. A linear concentration range was observed from 0.07 to 0.6mM, a limit of detection being 0.038 mM and a response time - 10s. The developed biosensor demonstrated good storage stability. A laboratory prototype of the proposed amperometric biosensor was applied to the samples of three commercial pharmaceuticals ("Tivortin", "Cytrarginine", "Aminoplazmal 10% E") for L-Arg testing. The obtained L-Arg-content values correlated well with those declared by producers. Copyright © 2012 Elsevier B.V. All rights reserved.

Growth and characterization of pure and doped NLO L-arginine ...

Indian Academy of Sciences (India)

Administrator

NLO; SHG; solution growth; LAA. 1. Introduction. L-arginine phosphate monohydrate (LAP) was first repor- ted by Xu et al (1983) as a promising nonlinear optical. (NLO) material. LAP is nearly three times more nonlinear than KDP. Monaco et al (1987) reported the formation of. LAP and its chemical analogs from the strongly ...

The DEAD-Box Protein CYT-19 Uses Arginine Residues in Its C-Tail To Tether RNA Substrates.

Science.gov (United States)

Busa, Veronica F; Rector, Maxwell J; Russell, Rick

2017-07-18

DEAD-box proteins are nonprocessive RNA helicases that play diverse roles in cellular processes. The Neurospora crassa DEAD-box protein CYT-19 promotes mitochondrial group I intron splicing and functions as a general RNA chaperone. CYT-19 includes a disordered, arginine-rich "C-tail" that binds RNA, positioning the helicase core to capture and unwind nearby RNA helices. Here we probed the C-tail further by varying the number and positions of arginines within it. We found that removing sets of as few as four of the 11 arginines reduced RNA unwinding activity (k cat /K M ) to a degree equivalent to that seen upon removal of the C-tail, suggesting that a minimum or "threshold" number of arginines is required. In addition, a mutant with 16 arginines displayed RNA unwinding activity greater than that of wild-type CYT-19. The C-tail modifications impacted unwinding only of RNA helices within constructs that included an adjacent helix or structured RNA element that would allow C-tail binding, indicating that the helicase core remained active in the mutants. In addition, changes in RNA unwinding efficiency of the mutants were mirrored by changes in functional RNA affinity, as determined from the RNA concentration dependence of ATPase activity, suggesting that the C-tail functions primarily to increase RNA affinity. Interestingly, the salt concentration dependence of RNA unwinding activity is unaffected by C-tail composition, suggesting that the C-tail uses primarily hydrogen bonding, not electrostatic interactions, to bind double-stranded RNA. Our results provide insights into how an unstructured C-tail contributes to DEAD-box protein activity and suggest parallels with other families of RNA- and DNA-binding proteins.

Agmatine: multifunctional arginine metabolite and magic bullet in clinical neuroscience?

Science.gov (United States)

Laube, Gregor; Bernstein, Hans-Gert

2017-07-26

Agmatine, the decarboxylation product of arginine, was largely neglected as an important player in mammalian metabolism until the mid-1990s, when it was re-discovered as an endogenous ligand of imidazoline and α 2 -adrenergic receptors. Since then, a wide variety of agmatine-mediated effects have been observed, and consequently agmatine has moved from a wallflower existence into the limelight of clinical neuroscience research. Despite this quantum jump in scientific interest, the understanding of the anabolism and catabolism of this amine is still vague. The purification and biochemical characterization of natural mammalian arginine decarboxylase and agmatinase still are open issues. Nevertheless, the agmatinergic system is currently one of the most promising candidates in order to pharmacologically interfere with some major diseases of the central nervous system, which are summarized in the present review. Particularly with respect to major depression, agmatine, its derivatives, and metabolizing enzymes show great promise for the development of an improved treatment of this common disease. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Arginine and Polyamines Fate in Leishmania Infection

Science.gov (United States)

Muxel, Sandra M.; Aoki, Juliana I.; Fernandes, Juliane C. R.; Laranjeira-Silva, Maria F.; Zampieri, Ricardo A.; Acuña, Stephanie M.; Müller, Karl E.; Vanderlinde, Rubia H.; Floeter-Winter, Lucile M.

2018-01-01

Leishmania is a protozoan parasite that alternates its life cycle between the sand fly and the mammalian host macrophages, involving several environmental changes. The parasite responds to these changes by promoting a rapid metabolic adaptation through cellular signaling modifications that lead to transcriptional and post-transcriptional gene expression regulation and morphological modifications. Molecular approaches such as gene expression regulation, next-generation sequencing (NGS), microRNA (miRNA) expression profiling, in cell Western blot analyses and enzymatic activity profiling, have been used to characterize the infection of murine BALB/c and C57BL/6 macrophages, as well as the human monocytic cell-lineage THP-1, with Leishmania amazonensis wild type (La-WT) or arginase knockout (La-arg-). These models are being used to elucidate physiological roles of arginine and polyamines pathways and the importance of arginase for the establishment of the infection. In this review, we will describe the main aspects of Leishmania-host interaction, focusing on the arginine and polyamines pathways and pointing to possible targets to be used for prognosis and/or in the control of the infection. The parasite enzymes, arginase and nitric oxide synthase-like, have essential roles in the parasite survival and in the maintenance of infection. On the other hand, in mammalian macrophages, defense mechanisms are activated inducing alterations in the mRNA, miRNA and enzymatic profiles that lead to the control of infection. Furthermore, the genetic background of both parasite and host are also important to define the fate of infection. PMID:29379478

Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

Directory of Open Access Journals (Sweden)

Takashi Kondoh

2010-06-01

Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers

DEFF Research Database (Denmark)

Lenz, Elisabeth; Löbmann, Korbinian; Rades, Thomas

2017-01-01

Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying......, and stability. Results were compared to those of spray-dried formulations with the same compositions and to spray-dried indomethacin-copovidone. Overall, stable co-amorphous systems could be prepared by extrusion without or with copovidone, which exhibited comparable molecular interaction properties...... to the respective spray-dried products, while phase separation was detected by differential scanning calorimetry in several cases. The formulations containing indomethacin in combination with arginine and copovidone showed enhanced dissolution behavior over the formulations with only copovidone or arginine....

Sensitive radioimmunoassay for plasma arginine vasopressin

International Nuclear Information System (INIS)

Thibonnier, M.; Soto, M.E.; Corvol, P.; Milliez, P.; Marchetti, J.; Menard, J.

1980-01-01

Using an ion exchange resin, a sensitive radioimmunoassay for plasma arginine vasopressin (AVP) was developed. This assay was characterized by the absence of blank values, an excellent recovery rate, great sensitivity (0.1 pg of AVP was significantly detected) and reproducibility. In 8 normal men, plasma AVP after overnight dehydration was 1.57+-0.17 pg/ml, and dropped to 0.58+-0.11 pg/ml after 20 ml/kg oral water loading. Significant correlations between plasma AVP levels and plasma or urinary osmolality confirm the validity of this assay. In complete pituitary diabetes insipidus (n=4) plasma AVP was undetectable whereas it was frankly increased in Schwartz-Bartter syndrome (3 to 33 pg/ml, n=8) [fr

Quantitation of movement of the phosphoryl group during catalytic transfer in the arginine kinase reaction: 31P relaxation measurements on enzyme-bound equilibrium mixtures

International Nuclear Information System (INIS)

Ray, Bruce D.; Jarori, Gotam K.; Nageswara Rao, B.D.

2002-01-01

31 P nuclear spin relaxation measurements have been made on enzyme-bound equilibrium mixtures of lobster-muscle arginine kinase in the presence of substituent activating paramagnetic cation Co(II) (in place of Mg(II)), i.e., on samples in which the reaction, E·CoATP·arginine ↔ E·CoADP·P-arginine, is in progress. The results have been analyzed on the basis of a previously published theory (Nageswara Rao, B.D. (1995) J. Magn. Reson., B108, 289-293) to determine the structural changes in the reaction complex accompanying phosphoryl transfer. The analysis enables the determination of the change in the Co(II)- 31 P (γ-P(ATP)) vector as the transferable phosphoryl group moves over and attaches to arginine to form P-arginine. It is shown that the Co(II)- 31 P distance of ∼3.0 A, representing direct coordination of Co(II) to γ-P(ATP), changes to ∼4.0 A when P-arginine is formed in the enzyme-bound reaction complex. This elongation of the Co(II)- 31 P vector implies an excursion of at least 1.0 A for the itinerant phosphoryl group on the surface of the enzyme

The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis

DEFF Research Database (Denmark)

Molnar, Tihamer; Pusch, Gabriella; Papp, Viktoria

2014-01-01

BACKGROUND: Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone. METHODS: Patients with acute ischemic stroke (AIS, n = 55......) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy...... subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring. RESULTS: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting...

Unique contributions of an arginine side chain to ligand recognition in a glutamate-gated chloride channel

DEFF Research Database (Denmark)

Lynagh, Timothy; Komnatnyy, Vitaly V; Pless, Stephan A

2017-01-01

Glutamate recognition by neurotransmitter receptors often relies on arginine (Arg) residues in the binding site, leading to the assumption that charge-charge interactions underlie ligand recognition. However, assessing the precise chemical contribution of Arg side chains to protein function......-gated chloride channel from the nematode Haemonchus contortus. Our data unveil a surprisingly small contribution of charge at a conserved arginine side chain previously suggested to form a salt bridge with the ligand, glutamate. Instead, our data show that Arg contributes crucially to ligand sensitivity via...

Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

Science.gov (United States)

Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2017-06-25

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

PENGARUH BERBAGAI KECAMBAH KACANG-KACANGAN LOKAL SEBAGAI BAHAN DASAR MEAT ANALOG TERHADAP SIFAT FISIK (TEKSTUR, KESUKAAN DAN RASIO ARGININ/LISIN

Directory of Open Access Journals (Sweden)

Bayu Kanetro

2013-06-01

Full Text Available The aims of this research were to determine the best of local legume sprout as raw material of meat analog, based on its texture, sensory (preference properties, and the ratio of arginine/lysine, compared to meat analog from soybean. Meat analogs were made of protein of local legumes sprout, which were velvet beans, cowpeas, and winged beans that had been germinated for 48, 36 and 24 hr respectively. The protein of velvet beans, cowpeas, and winged beans sprout for meat analog production were extracted at pH 9 and precipitated at pH 4, 5, and 5 respectively. Hence their products were analyzed the texture, the sensory properties (the hedonic scales of color, texture, odor, taste, and overall, and the ratio of arginine/lysine. The characteristics of meat analog from the legumes sprout were compared to meat analog from soybean for determination of the best legume sprout as raw material of meat analog. The result of this research showed the properties of meat analog from winged bean and cowpeas sprouts were better than velvet beans sprout. The meat analog from soybean was still better than meat analog from the local legumes sprout, especially its texture. The arginine content, that was known as  hypocholesterolemic and hypoglycemic component,  of meat analog from cowpeas sprout was lower than meat analog from soybean, but its ratio of arginie/lysine was not signifi cantly different. While the ratio of arginine/lysine of meat analog from the other legumes sprout were lower than meat analog from soybean. Therefore the meat analog from cowpeas sprout was chosen as the best product and was potential as functional food especially for reducing blood cholesterol. Keywords: Meat analog, sprout, local legumes, arginine/lysine ratio   ABSTRAK Tujuan penelitian ini adalah untuk menentukan jenis kecambah kacang-kacangan lokal terbaik sebagai bahan baku kedelai berdasarkan tekstur, sifat sensoris, dan rasio arginin/lisin dibandingkan meat analog dari biji

Overexpression of arginase I in enterocytes of transgenic mice elicits a selective arginine deficiency and affects skin, muscle, and lymphoid development

NARCIS (Netherlands)

de Jonge, Wouter J.; Hallemeesch, Marcella M.; Kwikkers, Karin L.; Ruijter, Jan M.; de Gier-de Vries, Corrie; van Roon, Marian A.; Meijer, Alfred J.; Marescau, Bart; de Deyn, Peter P.; Deutz, Nicolaas E. P.; Lamers, Wouter H.

2002-01-01

BACKGROUND: Arginine is required for the detoxification of ammonia and the synthesis of proteins, nitric oxide, agmatine, creatine, and polyamines, and it may promote lymphocyte function. In suckling mammals, arginine is synthesized in the enterocytes of the small intestine, but this capacity is

Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model.

Science.gov (United States)

Edwards, Adam B; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P

2017-02-01

In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1-6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

Science.gov (United States)

Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

2012-01-01

Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

Effect of in ovo injection with L-arginine on productive and ...

African Journals Online (AJOL)

p2492989

Significant decreases were recorded in blood serum cholesterol, total lipids ... 2% and 3% arginine, resulted in a significant improvement in the productive ... Various factors play important roles in birds in influencing hatchability efficiency and growth ... in the yolk sac may not be sufficient to supply in the maintenance energy.

The Effect of Pumpkin ( Cucurbita pepo L) Seeds and L-Arginine ...

African Journals Online (AJOL)

The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on androgenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in ...

Thermal, FT–IR and SHG efficiency studies of L-arginine doped KDP ...

Indian Academy of Sciences (India)

TECS

popular due to their applications in frequency converters, electro-optic switching and .... parameters of dehydration process of pure and L-arginine doped KDP crystals were ... action, R a gas constant, and a the heating rate in deg.C.min. –1.

Feed supplementation with arginine and zinc on antioxidant status and inflammatory response in challenged weanling piglets

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Nadia Bergeron

2017-09-01

Full Text Available Although supplementing the diet with zinc oxide and arginine is known to improve growth in weanling piglets, the mechanism of action is not well understood. We measured the antioxidant status and inflammatory response in 48 weanling castrated male piglets fed diets supplemented with or without zinc oxide (2,500 mg Zn oxide per kg and arginine (1% starting at the age of 20 days. The animals were injected with lipopolysaccharide (100 μg/kg on day 5. Half of them received another injection on day 12. Blood samples were taken just before and 6, 24 and 48 h after injection and the mucosa lining the ileum was recovered following euthanizing on days 7 and 14. Zinc supplementation increased reduced and total glutathione (GSH (reduced and total during days 5 to 7 and arginine decreased oxidized GSH measured on days 5 and 12 and the ratio of total antioxidant capacity to total oxidative status during days 12 to 14. Zinc decreased plasma malondialdehyde measured on days 5 and 12 and serum haptoglobin measured on day 12 and increased both metallothionein-1 expression and total antioxidant capacity measured in the ileal mucosa on day 14. Tumour necrosis factor α concentration decreased from days 5 to 12 (all effects were significant at P < 0.05. This study shows that the zinc supplement reduced lipid oxidation and lipopolysaccharide-induced inflammation during the post-weaning period, while the arginine supplementation had only a limited effect.

A single arginine residue is required for the interaction of the electron transferring flavoprotein (ETF) with three of its dehydrogenase partners.

Science.gov (United States)

Parker, Antony R

2003-12-01

The interaction of several dehydrogenases with the electron transferring flavoprotein (ETF) is a crucial step required for the successful transfer of electrons into the electron transport chain. The exact determinants regarding the interaction of ETF with its dehydrogenase partners are still unknown. Chemical modification of ETF with arginine-specific reagents resulted in the loss, to varying degrees, of activity with medium chain acyl-coenzyme A dehydrogenase (MCAD). The kinetic profiles showed the inactivations followed pseudo-first-order kinetics for all reagents used. For activity with MCAD, maximum inactivation of ETF was accomplished by 2,3-butanedione (4% residual activity after 120 min) and it was shown that modification of one arginine residue was responsible for the inactivation. Almost 100% restoration of this ETF activity was achieved upon incubation with free arginine. However, the same 2,3-butanedione modified ETF only possessed decreased activity with dimethylglycine-(DMGDH, 44%) and sarcosine- (SDH, 27%) dehydrogenases unlike the abolition with MCAD. Full protection of ETF from arginine modification by 2,3-butanedione was achieved using substrate-protected DMGDH, MCAD and SDH respectively. Cross-protection studies of ETF with the three dehydrogenases implied use of the same single arginine residue in the binding of all three dehydrogenases. These results lead us to conclude that this single arginine residue is essential in the binding of the ETF to MCAD, but only contributes partially to the binding of ETF to SDH and DMGDH and thus, the determinants of the dehydrogenase binding sites overlap but are not identical.

Further studies of the effects of aging on arginine metabolites in the rat vestibular nucleus and cerebellum.

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Liu, P; Gupta, N; Jing, Y; Collie, N D; Zhang, H; Smith, P F

2017-04-21

Some studies have demonstrated that aging is associated with impaired vestibular reflexes, especially otolithic reflexes, resulting in postural instability. However, the neurochemical basis of these age-related changes is still poorly understood. The l-arginine metabolic system has been implicated in changes in the brain associated with aging. In the current study, we examined the levels of l-arginine and its metabolizing enzymes and downstream metabolites in the vestibular nucleus complex (VNC) and cerebellum (CE) of rats with and without behavioral testing which were young (4months old), middle-aged (12months old) or aged (24months old). We found that aging was associated with lower nitric oxide synthase activity in the CE of animals with testing and increased arginase in the VNC and CE of animals with testing. l-citrulline and l-ornithine were lower in the VNC of aged animals irrespective of testing, while l-arginine and l-citrulline were lower in the CE with and without testing, respectively. In the VNC and CE, aging was associated with lower levels of glutamate in the VNC, irrespective of testing. In the VNC it was associated with higher levels of agmatine and putrescine, irrespective of testing. In the CE, aging was associated with higher levels of putrescine in animals without testing and with higher levels of spermine in animals with testing, and spermidine, irrespective of testing. Multivariate analyses indicated significant predictive relationships between the different variables, and there were correlations between some of the neurochemical variables and behavioral measurements. Cluster analyses revealed that aging altered the relationships between l-arginine and its metabolites. The results of this study demonstrate that there are major changes occurring in l-arginine metabolism in the VNC and CE as a result of age, as well as behavioral activity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

Science.gov (United States)

Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

2013-12-01

Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

Hot Melt Extrusion and Spray Drying of Co-amorphous Indomethacin-Arginine With Polymers.

Science.gov (United States)

Lenz, Elisabeth; Löbmann, Korbinian; Rades, Thomas; Knop, Klaus; Kleinebudde, Peter

2017-01-01

Co-amorphous drug-amino acid systems have gained growing interest as an alternative to common amorphous formulations which contain polymers as stabilizers. Several preparation methods have recently been investigated, including vibrational ball milling on a laboratory scale or spray drying in a larger scale. In this study, the feasibility of hot melt extrusion for continuous manufacturing of co-amorphous drug-amino acid formulations was examined, challenging the fact that amino acids melt with degradation at high temperatures. Furthermore, the need for an addition of a polymer in this process was evaluated. After a polymer screening via the solvent evaporation method, co-amorphous indomethacin-arginine was prepared by a melting-solvent extrusion process without and with copovidone. The obtained products were characterized with respect to their solid-state properties, non-sink dissolution behavior, and stability. Results were compared to those of spray-dried formulations with the same compositions and to spray-dried indomethacin-copovidone. Overall, stable co-amorphous systems could be prepared by extrusion without or with copovidone, which exhibited comparable molecular interaction properties to the respective spray-dried products, while phase separation was detected by differential scanning calorimetry in several cases. The formulations containing indomethacin in combination with arginine and copovidone showed enhanced dissolution behavior over the formulations with only copovidone or arginine. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.

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Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Gapsys, Vytautas; Ucurum, Zöhre; de Groot, Bert L; Fotiadis, Dimitrios

2016-09-13

Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

The Role of Protein Arginine Methyltransferases in Inflammatory Responses

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Ji Hye Kim

2016-01-01

Full Text Available Protein arginine methyltransferases (PRMTs mediate the methylation of a number of protein substrates of arginine residues and serve critical functions in many cellular responses, including cancer development, progression, and aggressiveness, T-lymphocyte activation, and hepatic gluconeogenesis. There are nine members of the PRMT family, which are divided into 4 types (types I–IV. Although most PRMTs do not require posttranslational modification (PTM to be activated, fine-tuning modifications, such as interactions between cofactor proteins, subcellular compartmentalization, and regulation of RNA, via micro-RNAs, seem to be required. Inflammation is an essential defense reaction of the body to eliminate harmful stimuli, including damaged cells, irritants, or pathogens. However, chronic inflammation can eventually cause several types of diseases, including some cancers, atherosclerosis, rheumatoid arthritis, and periodontitis. Therefore, inflammation responses should be well modulated. In this review, we briefly discuss the role of PRMTs in the control of inflammation. More specifically, we review the roles of four PRMTs (CARM1, PRMT1, PRMT5, and PRMT6 in modulating inflammation responses, particularly in terms of modulating the transcriptional factors or cofactors related to inflammation. Based on the regulatory roles known so far, we propose that PRMTs should be considered one of the target molecule groups that modulate inflammatory responses.

The effect of pumpkin (Cucurbita pepo L) seeds and L-arginine supplementation on serum lipid concentrations in atherogenic rats.

Science.gov (United States)

Abuelgassim, Abuelgassim O; Al-showayman, Showayman I A

2012-01-01

The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on atherogenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in drinking water and the other supplemented with pumpkin seeds in diet at a concentration equivalent to 2% arginine. Supplementation continued for 37 days. Atherogenic rats supplemented with pumpkin seeds showed a significant decrease (ppumpkin seeds significantly decreased serum concentrations of TC and LDL-C. Our findings suggest that pumpkin seeds supplementation has a protective effect against atherogenic rats and this protective effect was not attributed to the high arginine concentrations in pumpkin seeds.

Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study

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Yaman F

2016-06-01

Full Text Available Ferhan Yaman,1 Izzet Acikan,1 Serkan Dundar,2 Sercan Simsek,3 Mehmet Gul,4 İbrahim Hanifi Ozercan,3 James Komorowski,5 Kazim Sahin6 1Department of Oral-Maxillofacial Surgery, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 2Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, Turkey; 3Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey; 4Department of Periodontology, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 5Nutrition 21, LLC, Purchase, NY, USA; 6Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Background: Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25% is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. Objective: The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. Methods: The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Results: Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05. New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05. However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05. Conclusion: ASI supplementation significantly improved bone tissue

Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation.

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Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

2018-03-01

Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N ω -nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

Cell surface binding and uptake of arginine- and lysine-rich penetratin peptides in absence and presence of proteoglycans

KAUST Repository

Åmand, Helene L.

2012-11-01

Cell surface proteoglycans (PGs) appear to promote uptake of arginine-rich cell-penetrating peptides (CPPs), but their exact functions are unclear. To address if there is specificity in the interactions of arginines and PGs leading to improved internalization, we used flow cytometry to examine uptake in relation to cell surface binding for penetratin and two arginine/lysine substituted variants (PenArg and PenLys) in wildtype CHO-K1 and PG-deficient A745 cells. All peptides were more efficiently internalized into CHO-K1 than into A745, but their cell surface binding was independent of cell type. Thus, PGs promote internalization of cationic peptides, irrespective of the chemical nature of their positive charges. Uptake of each peptide was linearly dependent on its cell surface binding, and affinity is thus important for efficiency. However, the gradients of these linear dependencies varied significantly. Thus each peptide\\'s ability to stimulate uptake once bound to the cell surface is reliant on formation of specific uptake-promoting interactions. Heparin affinity chromatography and clustering experiments showed that penetratin and PenArg binding to sulfated sugars is stabilized by hydrophobic interactions and result in clustering, whereas PenLys only interacts through electrostatic attraction. This may have implications for the molecular mechanisms behind arginine-specific uptake stimulation as penetratin and PenArg are more efficiently internalized than PenLys upon interaction with PGs. However, PenArg is also least affected by removal of PGs. This indicates that an increased arginine content not only improve PG-dependent uptake but also that PenArg is more adaptable as it can use several portals of entry into the cell. © 2012 Elsevier B.V.

Increased Erythrocytes By-Products of Arginine Catabolism Are Associated with Hyperglycemia and Could Be Involved in the Pathogenesis of Type 2 Diabetes Mellitus

Science.gov (United States)

Ramírez-Zamora, Serafín; Méndez-Rodríguez, Miguel L.; Olguín-Martínez, Marisela; Sánchez-Sevilla, Lourdes; Quintana-Quintana, Miguel; García-García, Norberto; Hernández-Muñoz, Rolando

2013-01-01

Diabetes mellitus (DM) is a worldwide disease characterized by metabolic disturbances, frequently associated with high risk of atherosclerosis and renal and nervous system damage. Here, we assessed whether metabolites reflecting oxidative redox state, arginine and nitric oxide metabolism, are differentially distributed between serum and red blood cells (RBC), and whether significant metabolism of arginine exists in RBC. In 90 patients with type 2 DM without regular treatment for diabetes and 90 healthy controls, paired by age and gender, we measured serum and RBC levels of malondialdehyde (MDA), nitrites, ornithine, citrulline, and urea. In isolated RBC, metabolism of L-[14C]-arginine was also determined. In both groups, nitrites were equally distributed in serum and RBC; citrulline predominated in serum, whereas urea, arginine, and ornithine were found mainly in RBC. DM patients showed hyperglycemia and increased blood HbA1C, and increased levels of these metabolites, except for arginine, significantly correlating with blood glucose levels. RBC were observed to be capable of catabolizing arginine to ornithine, citrulline and urea, which was increased in RBC from DM patients, and correlated with an increased affinity for arginine in the activities of putative RBC arginase (Km = 0.23±0.06 vs. 0.50±0.13 mM, in controls) and nitric oxide synthase (Km = 0.28±0.06 vs. 0.43±0.09 mM, in controls). In conclusion, our results suggest that DM alters metabolite distribution between serum and RBC, demonstrating that RBC regulate serum levels of metabolites which affect nitrogen metabolism, not only by transporting them but also by metabolizing amino acids such as arginine. Moreover, we confirmed that urea can be produced also by human RBC besides hepatocytes, being much more evident in RBC from patients with type 2 DM. These events are probably involved in the specific physiopathology of this disease, i.e., endothelial damage and dysfunction. PMID:23826148

Protective effect of chlorogenic acid on the inflammatory damage of pancreas and lung in mice with l-arginine-induced pancreatitis.

Science.gov (United States)

Ohkawara, Tatsuya; Takeda, Hiroshi; Nishihira, Jun

2017-12-01

Pancreatitis is characterized by inflammatory disease with severe tissue injury in pancreas, and the incidence of pancreatitis has been recently increasing. Although several treatments of acute pancreatitis have been developed, some patients have been resistant to current therapy. Chlorogenic acid (CGA) is one of the polyphenols, and is known to have an anti-inflammatory effect. In this study, we investigated the effects of CGA on experimental pancreatitis in mice. Pancreatitis was induced by twice injection of l-arginine (5g/kg body weight). Mice were intraperitoneally injected with CGA (20mg/kg or 40mg/kg) 1h before administration of l-arginine. Administration of 40mg/kg of CGA decreased the histological severity of pancreatitis and pancreatitis-associated lung injury. Moreover, administration of CGA inhibited the levels of pancreatic enzyme activity. Interestingly, CGA reduced the serum and pancreatic levels of macrophage migration inhibitory factor (MIF) in mice with l-arginine-induced pancreatitis. Our results suggest that CGA has an anti-inflammatory effect on l-arginine-induced pancreatitis and pancreatitis-associated lung injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Citrate and Arginine on Sorption of Nickel to Yazd Sepiolite and Calcite

Directory of Open Access Journals (Sweden)

Ahmadreza Sheikhhosseini

2017-03-01

Full Text Available Introduction: Pollution of soil and water environment by release of heavy metals is of great concerns of the last decades. Sorption of heavy metals by low cost materials is considered as an inexpensive and efficient method used for removal of heavy metals from soil-water systems. The presence of different ligands with various complexing abilities can change the sorption properties of heavy metals and their fate in the environment as well. In order to assess the effect of citrate and arginine as natural organic ligands in soil environment, in a batch study we investigated the effects of these ligands on equilibrium sorption of nickel to sepiolite and calcite minerals and also kinetics of Ni sorption by these minerals. Materials and Methods: Minerals used in this study included sepiolite from Yazd (Iran and pure calcite (Analytical grade, Merck, Germany. Sepiolite was purified, saturated with Ca using 0.5 M CaCl2, powdered in a mortar and sieved by non-metal 230 mesh standard wire sieve. For equilibrium sorption study, in a 50-mL polyethylene centrifuge tube,0.3 g sample of each mineral was suspended in 30 mL of a 0.01 M CaCl2 solution containing 0, 5, 10, 20, 40, 60, 80 and 100 mg L-1 Ni (NiCl2 and containing zero (as control or 0.1mmol L-1 citrate or arginine ligands. The applied concentrationsfor each ligand can naturally occur in soils. Preparedtubes were shaken (180±2 rpm, 25±1oC for 24 h using an orbital shaker and centrifuged (4000×g for 10 min and the supernatants were analyzed for Ni concentration using an atomic absorption spectrophotometer (AAnalyst 200 Perkin-Elmer at a wavelength of 232 nm and a detection limit of 0.05 mg L-1. The quantity of Ni retained by each mineral at equilibrium was calculated using equation qe = (Ci - CeV/W where qe was the amount of nickel retained by mineral surface at equilibrium. Ci and Ce were the initial and the equilibrium concentrations (mg L-1 of Ni, respectively, V was the volume (L of the solution

Periodical low eggshell temperatures during incubation and post hatch dietary arginine supplementation

NARCIS (Netherlands)

Afsarian, O.; Shahir, M.H.; Akhlaghi, A.; Lotfolahian, H.; Hoseini, A.; Lourens, A.

2016-01-01

An experiment was conducted to evaluate the effects of a periodically low eggshell temperature exposure during incubation and dietary supplementation of arginine on performance, ascites incidence, and cold tolerance acquisition in broilers. A total of 2,400 hatching eggs were randomly assigned to

Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice.

Science.gov (United States)

Ito, Tatsuo; Kubo, Masayuki; Nagaoka, Kenjiro; Funakubo, Narumi; Setiawan, Heri; Takemoto, Kei; Eguchi, Eri; Fujikura, Yoshihisa; Ogino, Keiki

2018-02-01

Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO 2 - were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO 2 - levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO 2 - levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

Unidirectional growth and characterization of L-arginine monohydrochloride monohydrate single crystals

International Nuclear Information System (INIS)

Sangeetha, K.; Babu, R. Ramesh; Bhagavannarayana, G.; Ramamurthi, K.

2011-01-01

Highlights: → L-Arginine monohydrochloride monohydrate (LAHCl) single crystal was grown successfully by unidirectional solution growth method for the first time. → High crystalline perfection was observed for UDS grown crystal compared to CS grown crystal. → The optical transparency and mechanical stability are high for UDS grown LAHCl single crystal. → Optical birefringence measurement on this material. → The piezoelectric resonance frequencies observation - first time observation on this material. - Abstract: L-Arginine monohydrochloride monohydrate (LAHCl) single crystals were grown successfully by conventional and unidirectional solution growth methods. The crystalline perfection of grown crystals was analyzed by high-resolution X-ray diffraction. The linear optical transmittance, mechanical stability of conventional and unidirectional grown LAHCl single crystals were analyzed and compared along (0 0 1) plane. The refractive index and birefringence of LAHCl single crystals were also measured using He-Ne laser source. From the dielectric studies, piezoelectric resonance frequencies were observed in kHz frequency range for both conventional and unidirectional grown LAHCl single crystals along (0 0 1) plane.

Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

DEFF Research Database (Denmark)

Nielsen, J.R.; Hansen, Harald S.; Jensen, B.

1987-01-01

Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

[Construction of Corynebacterium crenatum AS 1.542 δ argR and analysis of transcriptional levels of the related genes of arginine biosynthetic pathway].

Science.gov (United States)

Chen, Xuelan; Tang, Li; Jiao, Haitao; Xu, Feng; Xiong, Yonghua

2013-01-04

ArgR, coded by the argR gene from Corynebacterium crenatum AS 1.542, acts as a negative regulator in arginine biosynthetic pathway. However, the effect of argR on transcriptional levels of the related biosynthetic genes has not been reported. Here, we constructed a deletion mutant of argR gene: C. crenatum AS 1.542 Delta argR using marker-less knockout technology, and compared the changes of transcriptional levels of the arginine biosynthetic genes between the mutant strain and the wild-type strain. We used marker-less knockout technology to construct C. crenatum AS 1.542 Delta argR and analyzed the changes of the relate genes at the transcriptional level using real-time fluorescence quantitative PCR. C. crenatum AS 1.542 Delta argR was successfully obtained and the transcriptional level of arginine biosynthetic genes in this mutant increased significantly with an average of about 162.1 folds. The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR. However, the deletion of this regulator does not result in a clear change in arginine production in the bacteria.

Ni(II) complexes of arginine Schiff-bases and its interaction with DNA

Energy Technology Data Exchange (ETDEWEB)

Sallam, S.A., E-mail: shehabsallam@yahoo.com [Chemistry Department, Faculty of Science, Suez Canal University, Isamilia (Egypt); Abbas, A.M. [Chemistry Department, Faculty of Science, Suez Canal University, Isamilia (Egypt)

2013-04-15

Ni(II) complexes with Schiff-bases obtained by condensation of arginine with salicylaldehyde; 2,3-; 2,4-; 2,5-dihydroxybenzaldehyde and o-hydroxynaphthaldehyde have been synthesized using the template method in ethanol or ammonia media. They were characterized by elemental analyses, conductivity measurements, magnetic moment, UV, IR and {sup 1}H NMR spectra as well as thermal analysis (TG, DTG and DTA). The Schiff-bases are dibasic tridentate donors and the complexes have diamagnetic square planar and octahedral structures. The complexes decompose in three steps where kinetic and thermodynamic parameters of the decomposition steps were computed. The interactions of the formed complexes with FM-DNA were monitored by UV and fluorescence spectroscopy. -- Highlights: ► Arginine Schiff-bases and their nickel(II) complexes have been synthesized. ► Magnetic and spectral data show diamagnetic square planar and octahedral complexes. ► The complexes thermally decompose in three stages. Interaction with FM-DNA shows hyperchromism with blue shift.

Ni(II) complexes of arginine Schiff-bases and its interaction with DNA

International Nuclear Information System (INIS)

Sallam, S.A.; Abbas, A.M.

2013-01-01

Ni(II) complexes with Schiff-bases obtained by condensation of arginine with salicylaldehyde; 2,3-; 2,4-; 2,5-dihydroxybenzaldehyde and o-hydroxynaphthaldehyde have been synthesized using the template method in ethanol or ammonia media. They were characterized by elemental analyses, conductivity measurements, magnetic moment, UV, IR and 1 H NMR spectra as well as thermal analysis (TG, DTG and DTA). The Schiff-bases are dibasic tridentate donors and the complexes have diamagnetic square planar and octahedral structures. The complexes decompose in three steps where kinetic and thermodynamic parameters of the decomposition steps were computed. The interactions of the formed complexes with FM-DNA were monitored by UV and fluorescence spectroscopy. -- Highlights: ► Arginine Schiff-bases and their nickel(II) complexes have been synthesized. ► Magnetic and spectral data show diamagnetic square planar and octahedral complexes. ► The complexes thermally decompose in three stages. Interaction with FM-DNA shows hyperchromism with blue shift

Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine

DEFF Research Database (Denmark)

Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev

2015-01-01

–arginine in a larger production scale. In this work, a tablet formulation was developed for a co-amorphous salt, namely spray dried indomethacin–arginine (SD IND–ARG). The effects of compaction pressure on tablet properties, physical stability and dissolution profiles under non-sink conditions were examined....... Dissolution profiles of tablets with SD IND–ARG (TAB SD IND–ARG) were compared to those of tablets containing a physical mixture of crystalline IND and ARG (TAB PM IND–ARG) and to the dissolution of pure spray dried powder. Concerning tableting, the developed formulation allowed for the preparation of tablets...... with a broad range of compaction pressures resulting in different porosities and tensile strengths. XRPD results showed that, overall, no crystallization occurred neither during tableting nor during long-term storage. Dissolution profiles of TAB SD IND–ARG showed an immediate release of IND by erosion...

Quantitation of movement of the phosphoryl group during catalytic transfer in the arginine kinase reaction: {sup 31}P relaxation measurements on enzyme-bound equilibrium mixtures

Energy Technology Data Exchange (ETDEWEB)

Ray, Bruce D. [Indiana University, Purdue University at Indianapolis (IUPUI), Department of Physics (United States); Jarori, Gotam K. [Tata Institute of Fundamental Research (India); Nageswara Rao, B.D. [Indiana University, Purdue University at Indianapolis (IUPUI), Department of Physics (United States)], E-mail: brao@iupui.edu

2002-05-15

{sup 31}P nuclear spin relaxation measurements have been made on enzyme-bound equilibrium mixtures of lobster-muscle arginine kinase in the presence of substituent activating paramagnetic cation Co(II) (in place of Mg(II)), i.e., on samples in which the reaction, E{center_dot}CoATP{center_dot}arginine {r_reversible} E{center_dot}CoADP{center_dot}P-arginine, is in progress. The results have been analyzed on the basis of a previously published theory (Nageswara Rao, B.D. (1995) J. Magn. Reson., B108, 289-293) to determine the structural changes in the reaction complex accompanying phosphoryl transfer. The analysis enables the determination of the change in the Co(II)-{sup 31}P ({gamma}-P(ATP)) vector as the transferable phosphoryl group moves over and attaches to arginine to form P-arginine. It is shown that the Co(II)-{sup 31}P distance of {approx}3.0 A, representing direct coordination of Co(II) to {gamma}-P(ATP), changes to {approx}4.0 A when P-arginine is formed in the enzyme-bound reaction complex. This elongation of the Co(II)-{sup 31}P vector implies an excursion of at least 1.0 A for the itinerant phosphoryl group on the surface of the enzyme.

Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine.

Science.gov (United States)

Berninger, Teresa; Bliem, Christina; Piccinini, Esteban; Azzaroni, Omar; Knoll, Wolfgang

2018-09-15

Herein, a biosensor based on a reduced graphene oxide field effect transistor (rGO-FET) functionalized with the cascading enzymes arginase and urease was developed for the detection of L-arginine. Arginase and urease were immobilized on the rGO-FET sensing surface via electrostatic layer-by-layer assembly using polyethylenimine (PEI) as cationic building block. The signal transduction mechanism is based on the ability of the cascading enzymes to selectively perform chemical transformations and prompt local pH changes, that are sensitively detected by the rGO-FET. In the presence of L-arginine, the transistors modified with (PEI/urease(arginase)) multilayers showed a shift in the Dirac point due to the change in the local pH close to the graphene surface, produced by the catalyzed urea hydrolysis. The transistors were able to monitor L-arginine in the 10-1000 μM linear range with a LOD of 10 μM, displaying a fast response and a good long-term stability. The sensor showed stereospecificity and high selectivity in the presence of non-target amino acids. Taking into account the label-free, real-time measurement capabilities and the easily quantifiable, electronic output signal, this biosensor offers advantages over state-of-the-art L-arginine detection methods. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Arginine metabolism is altered in adults with A-B + ketosis-prone diabetes

Science.gov (United States)

A-B + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible B cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. The objective of this study was to determine the relation be...

Insulin-increased L-arginine transport requires A(2A adenosine receptors activation in human umbilical vein endothelium.

Directory of Open Access Journals (Sweden)

Enrique Guzmán-Gutiérrez

Full Text Available Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1. This process involves the activation of A(2A adenosine receptors (A(2AAR in human umbilical vein endothelial cells (HUVECs. Insulin increases hCAT-1 activity and expression in HUVECs, and A(2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A(2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR, and SLC7A1 (for hCAT-1 reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K(m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1(-1606 or pGL3-hCAT-1(-650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1(-1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase

Energy Technology Data Exchange (ETDEWEB)

Debler, Erik W.; Jain, Kanishk; Warmack, Rebeccah A.; Feng, You; Clarke, Steven G.; Blobel, Günter; Stavropoulos, Pete

2016-02-08

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-L-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.

Heterologous radioimmunoassay for arginine vasopressin

International Nuclear Information System (INIS)

Shimamoto, K.; Murase, T.; Yamaji, T.

1976-01-01

A sensitive and specific radioimmunoassay for arginine vasopressin (AVP) was developed utilizing the antisera against lysine vasopressin (LVP) in combination with a labeled AVP. The assay employs an acetone extraction procedure and detects as little as 0.8 pg. per millimeter of AVP in human plasma. In normal subjects, the mean (+- S.D.) plasma concentration of AVP was 4.9 +- 1.2 pg. per milliliter after fluid deprivation and 1.2 +- 0.4 pg. per milliliter after water loading. Plasma AVP levels correlated significantly with plasma osmolalities. In four patients with diabetes insipidus, plasma AVP concentrations ranged from less than 0.8 to 1.2 pg. per milliliter, whereas six patients with the syndrome of inappropriate ADH secretion showed plasma levels of AVP which correspond to those of the dehydrated state in normal subjects or greater, although plasma osmolalities were low in all cases. It was concluded that the present radioimmunoassay method for AVP provides a useful way of assessing neurohypophyseal function in man

Arginine and proline applied as food additives stimulate high freeze tolerance in larvae of Drosophila melanogaster.

Science.gov (United States)

Koštál, Vladimír; Korbelová, Jaroslava; Poupardin, Rodolphe; Moos, Martin; Šimek, Petr

2016-08-01

The fruit fly Drosophila melanogaster is an insect of tropical origin. Its larval stage is evolutionarily adapted for rapid growth and development under warm conditions and shows high sensitivity to cold. In this study, we further developed an optimal acclimation and freezing protocol that significantly improves larval freeze tolerance (an ability to survive at -5°C when most of the freezable fraction of water is converted to ice). Using the optimal protocol, freeze survival to adult stage increased from 0.7% to 12.6% in the larvae fed standard diet (agar, sugar, yeast, cornmeal). Next, we fed the larvae diets augmented with 31 different amino compounds, administered in different concentrations, and observed their effects on larval metabolomic composition, viability, rate of development and freeze tolerance. While some diet additives were toxic, others showed positive effects on freeze tolerance. Statistical correlation revealed tight association between high freeze tolerance and high levels of amino compounds involved in arginine and proline metabolism. Proline- and arginine-augmented diets showed the highest potential, improving freeze survival to 42.1% and 50.6%, respectively. Two plausible mechanisms by which high concentrations of proline and arginine might stimulate high freeze tolerance are discussed: (i) proline, probably in combination with trehalose, could reduce partial unfolding of proteins and prevent membrane fusions in the larvae exposed to thermal stress (prior to freezing) or during freeze dehydration; (ii) both arginine and proline are exceptional among amino compounds in their ability to form supramolecular aggregates which probably bind partially unfolded proteins and inhibit their aggregation under increasing freeze dehydration. © 2016. Published by The Company of Biologists Ltd.

Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

2013-04-15

The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

Science.gov (United States)

Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

2013-04-01

The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations.

Science.gov (United States)

Riedel, E; Hampl, H; Steudle, V; Nündel, M

1996-01-01

Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p calcium alpha-ketoglutarate administration.

Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases

NARCIS (Netherlands)

T.B. van Dijk (Thamar); N. Gillemans (Nynke); C. Stein (Claudia); P. Fanis (Pavlos); J.A.A. Demmers (Jeroen); M.P.C. van de Corput (Mariëtte); J. Essers (Jeroen); F.G. Grosveld (Frank); U.M. Bauer (Uta-Maria); J.N.J. Philipsen (Sjaak)

2010-01-01

textabstractWe describe the isolation and characterization of Friend of Prmt1 (Fop), a novel chromatin target of protein arginine methyltransferases. Human Fop is encoded by C1orf77, a gene of previously unknown function. We show that Fop is tightly associated with chromatin, and that it is modified

Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

NARCIS (Netherlands)

Ravenscroft, T.A.; Baker, M.C.; Rutherford, N.J.; Neumann, M.; Mackenzie, I.R.; Josephs, K.A.; Boeve, B.F.; Petersen, R.; Halliday, G.M.; Kril, J.; van Swieten, J.C.; Seeley, W.W.; Dickson, D.W.; Rademakers, R.

2013-01-01

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent

Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

Science.gov (United States)

Gangula, P R; Wimalawansa, S J; Yallampalli, C

1997-04-01

We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

Arginine-esterase activity of kallikrein in the sera of whole-body irradiated rats and guinea-pigs

Energy Technology Data Exchange (ETDEWEB)

Pouckova, P; Pospisil, J; Dienstbier, Z [Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav

1977-09-01

In whole-body irradiated rats (800 R=LDsub(50/30)) and guinea pigs (300 R=LDsub(50/30)) changes were investigated in the arginine esterase activity of kallikrein in native serum as well as in serum exposed to contact with a clay suspension. From the values obtained the activity of prekallikrein was calculated. While in the rat serum significant changes in the arginine esterase activity of kallikrein were found, in the guinea pig serum the kallikrein activity did not change markedly. The activity of prekallikrein immediately after irradiation assumes a similar course in both types of laboratory animals while during later intervals a reverse pattern was observed.

Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells.

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Manca, Antonella; Sini, Maria Cristina; Izzo, Francesco; Ascierto, Paolo A; Tatangelo, Fabiana; Botti, Gerardo; Gentilcore, Giusy; Capone, Marilena; Mozzillo, Nicola; Rozzo, Carla; Cossu, Antonio; Tanda, Francesco; Palmieri, Giuseppe

2011-06-01

Arginine deiminase (ADI), an arginine-degrading enzyme, has been used in the treatment of tumours sensitive to arginine deprivation, such as malignant melanoma (MM) and hepatocellular carcinoma (HCC). Endogenous production of arginine is mainly dependent on activity of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) enzymes. We evaluated the effect of ADI treatment on OTC and ASS expression in a series of melanoma cell lines. Twenty-five primary melanoma cell lines and normal fibroblasts as controls underwent cell proliferation assays and Western blot analyses in the presence or absence of ADI. Tissue sections from primary MMs (N = 20) and HCCs (N = 20) were investigated by immunohistochemistry for ASS expression. Overall, 21/25 (84%) MM cell lines presented a cell growth inhibition by ADI treatment; none of them presented constitutive detectable levels of the ASS protein. However, 7/21 (33%) ADI-sensitive melanoma cell lines presented markedly increased expression levels of the ASS protein following ADI treatment, with a significantly higher IC50 median value. Growth was not inhibited and the IC50 was not reached among the remaining 4/25 (16%) MM cell lines; all of them showed constitutive ASS expression. The OTC protein was found expressed in all melanoma cell lines before and after the ADI treatment. Lack of ASS immunostaining was observed in all analyzed in vivo specimens. Our findings suggest that response to ADI treatment in melanoma is significantly correlated with the ability of cells to express ASS either constitutively at basal level (inducing drug resistance) or after the treatment (reducing sensitivity to ADI).

Action of arginine for protection of ulcerative colitis by dextran sodium sulphate (DSS); Acao da arginina na protecao da colite ulcerativa induzida por sulfato de sodio dextrano

Energy Technology Data Exchange (ETDEWEB)

Andrade, Maria Emilia Rabelo

2016-10-01

Recent studies have demonstrated the benefits of immunomodulators, such as arginine, in the regulation of inflammatory responses and trophism of the intestinal mucosa. The aim of this study was to evaluate the possible mechanisms action of arginine (pretreatment or treatment) in experimental model of ulcerative colitis induced by dextran sodium sulfate (DSS). C57BL/6 mice were randomized into 5 groups: Control group (C): standard diet and water; Arginine group (ARG): diet supplementation with arginine and water; Colitis group (COL): standard diet and DSS solution; Pretreated group (PT): diet supplementation with arginine before and during colitis induction; Treated group (T): diet supplementation with arginine during colitis induction. Colitis was induced by administration of 1.5% DSS for 5 days. After this, all the mice were euthanized and blood, organs and intestinal fluid were collected for carrying out analyzes. Parameters such as intestinal permeability (IP), bacterial translocation (BT), histological analysis (histological score, morphometric analysis, collagen and mucins stain), nitrate and nitrite, cytokines and chemokines, secretory immunoglobulin A (sIgA), inflammatory infiltrate and oxidative stress were performed. The ARG group did not show difference compared to group C in the investigated parameters (C vs ARG: p> 0.05). The COL group showed increased IP (C vs COL: p < 0.05) and BT (C vs COL: p <0.05). In the histological analysis, the COL group showed severe inflammation and reduction the crypts length. In addition, in the group COL observed increase infiltration of eosinophils, neutrophils and macrophages in the colon, increase cytokine IL-17 and chemokine KC in serum and oxidative stress in the colon (COL vs C: p <0.05). In the arginine-supplemented groups (PT and T) was observed decrease IP and BT to blood, liver and lung (PT and T vs Col: p <0.05). Histological analysis showed that the arginine (PT and T) preserved the intestinal mucosa and crypts

Antiviral and Virucidal Activities of N-Cocoyl-L-Arginine Ethyl Ester

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Hisashi Yamasaki

2011-01-01

Full Text Available Various amino acid-derived compounds, for example, Nα-Cocoyl-L-arginine ethyl ester (CAE, alkyloxyhydroxylpropylarginine, arginine cocoate, and cocoyl glycine potassium salt (Amilite, were examined for their virucidal activities against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, influenza A virus (IAV, and poliovirus type 1 (PV-1 in comparison to benzalkonium chloride (BKC and sodium dodecylsulfate (SDS as a cationic and anionic control detergent and also to other commercially available disinfectants. While these amino acid-derived compounds were all effective against HSV-1 and HSV-2, CAE and Amilite were the most effective. These two compounds were, however, not as effective against IAV, another enveloped virus, as against HSV. Cytotoxicity of CAE was weak; at 0.012%, only 5% of the cells were killed under the conditions, in which 100% cells were killed by either SDS or BKC. In addition to these direct virucidal effects, CAE inhibited the virus growth in the HSV-1- or PV-1-infected cells even at 0.01%. These results suggest a potential application of CAE as a therapeutic or preventive medicine against HSV superficial infection at body surface.

Arginine and antioxidant supplement on performance in elderly male cyclists: a randomized controlled trial

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Carpenter Catherine L

2010-03-01

Full Text Available Abstract Background Human exercise capacity declines with advancing age. These changes often result in loss of physical fitness and more rapid senescence. Nitric oxide (NO has been implicated in improvement of exercise capacity through vascular smooth muscle relaxation in both coronary and skeletal muscle arteries, as well as via independent mechanisms. Antioxidants may prevent nitric oxide inactivation by oxygen free radicals. The purpose of this study was to investigate the effects of an L-arginine and antioxidant supplement on exercise performance in elderly male cyclists. Methods This was a two-arm prospectively randomized double-blinded and placebo-controlled trial. Sixteen male cyclists were randomized to receive either a proprietary supplement (Niteworks®, Herbalife International Inc., Century City, CA or a placebo powder. Exercise parameters were assessed by maximal incremental exercise testing performed on a stationary cycle ergometer using breath-by-breath analysis at baseline, week one and week three. Results There was no difference between baseline exercise parameters. In the supplemented group, anaerobic threshold increased by 16.7% (2.38 ± 0.18 L/min, p 2 max between control and intervention groups at either week 1 or week 3 by comparison to baseline. Conclusion An arginine and antioxidant-containing supplement increased the anaerobic threshold at both week one and week three in elderly cyclists. No effect on VO2 max was observed. This study indicated a potential role of L-arginine and antioxidant supplementation in improving exercise performance in elderly.

Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles.

Science.gov (United States)

Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I; Penna, Mario

2017-01-01

Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens-amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT's social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT's many effects on behavior.

Selective small-chemical inhibitors of protein arginine methyltransferase 5 with anti-lung cancer activity.

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Gui-Mei Kong

Full Text Available Protein arginine methyltransferase 5 (PRMT5 plays critical roles in a wide variety of biological processes, including tumorigenesis. By screening a library of small chemical compounds, we identified eight compounds that selectively inhibit the PRMT5 enzymatic activity, with IC50 values ranging from 0.1 to 6 μM. Molecular docking simulation and site-directed mutagenesis indicated that identified compounds target the substrate-binding site in PRMT5. Treatment of lung cancer cells with identified inhibitors led to inhibition of the symmetrical arginine methylation of SmD3 and histones and the cellular proliferation. Oral administration of the inhibitor demonstrated antitumor activity in a lung tumor xenograft model. Thus, identified PRMT5-specific small-molecule inhibitors would help elucidate the biological roles of PRMT5 and serve as lead compounds for future drug development.

Low dose vitamin C, vitamin E or L-arginine supplementation and ...

African Journals Online (AJOL)

The effect of chronic low-dose supplementation with vitamin C (300mg/day for 6 weeks in adults or 100mg/day for 6 weeks in children) or vitamin E (100 IU/day for 6 weeks in adults) or L-Arginine (1g/day for 6 weeks in adults) in ameliorating the pathophysiology and combating the deleterious effects of sickle cell disease in ...

24-Hour protein, arginine and citrulline metabolism in fed critically ill children – a stable isotope tracer study

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de Betue, Carlijn T.I.; Garcia Casal, Xiomara C.; van Waardenburg, Dick A.; Schexnayder, Stephen M.; Joosten, Koen F.M.; Deutz, Nicolaas E.P.; Engelen, Marielle P.K.J.

2017-01-01

Background & aims The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4–8h) time period and extrapolate results to 24-hour. However, 24-hour measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-hour appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. Methods In eight critically ill children, admitted to the pediatric (n=4) or cardiovascular (n=4) intensive care unit, aged 0–10 years, receiving continuous (par)enteral nutrition with protein intake 1.0–3.7 g/kg/day, a 24-hour stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour. Results Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14–19% for intravenous tracers and 23–26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-hour level of whole body protein balance differed per individual. Conclusions In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. PMID:28089618

L-Arginine Pathway in COPD Patients with Acute Exacerbation

DEFF Research Database (Denmark)

Ruzsics, Istvan; Nagy, Lajos; Keki, Sandor

2016-01-01

-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects. RESULTS: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p ....001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p

Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat.

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Abd-Elrazek, A M; Ahmed-Farid, O A H

2018-02-01

Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase-3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L-arginine and L-carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by caspase-3. Administration of L-arg and L-car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy. © 2017 Blackwell Verlag GmbH.

Dependence of the expression of the radiation-induced gene conversion to arginine independence in diploid yeast on the amino acid concentration: effect on allelic mapping

International Nuclear Information System (INIS)

Murthy, M.S.S.; Rao, B.S.; Deorukhakar, V.V.

1976-01-01

The yield of radiation-induced gene conversion to arginine independence in diploid yeast depended on the concentration of the amino acid both in the plating medium and in the intracellular pool. By depletion of the level of arginine in the intracellular pool of amino acid or by provision of arginine at 0.4 mg/l of the plating medium, the yield was varied by a factor as high as 20. This may be important in studies of the genetic mapping of alleles based on the slope of conversion frequency versus dose line

Crystallization of dicalcium phosphate dihydrate with presence of glutamic acid and arginine at 37 °C.

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Li, Chengfeng; Ge, Xiaolu; Li, Guochang; Bai, Jiahai; Ding, Rui

2014-08-01

The formations of non-metabolic stones, bones and teeth were seriously related to the morphology, size and surface reactivity of dicalcium phosphate dihydrate (DCPD). Herein, a facile biomimetic mineralization method with presence of glutamic acid and arginine was employed to fabricate DCPD with well-defined morphology and adjustable crystallite size. In reaction solution containing more arginine, crystallization of DCPD occurred with faster rate of nucleation and higher density of stacked layers due to the generation of more OH(-) ions after hydrolysis of arginine at 37 °C. With addition of fluorescein or acetone, the consumption of OH(-) ions or desolvation reaction of Ca(2+) ions was modulated, which resulted in the fabrication of DCPD with adjustable crystallite sizes and densities of stacked layers. In comparison with fluorescein-loading DCPD, dicalcium phosphate anhydrate was prepared with enhanced photoluminescence properties due to the reduction of self-quenching effect and regular arrangement of encapsulated fluorescein molecules. With addition of more acetone, DCPD was prepared with smaller crystallite size via antisolvent crystallization. The simulated process with addition of amino acids under 37 °C would shed light on the dynamic process of biomineralization for calcium phosphate compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

Methyl salicylate-induced arginine catabolism is associated with up-regulation of polyamine and nitric oxide levels and improves chilling tolerance in cherry tomato fruit.

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Zhang, Xinhua; Shen, Lin; Li, Fujun; Meng, Demei; Sheng, Jiping

2011-09-14

The effects of methyl salicylate (MeSA) on chilling injury (CI) and gene expression levels, enzyme activities, and metabolites related to arginine catabolism in cherry tomato fruit were investigated. Freshly harvested fruits were treated with 0.05 mM MeSA vapor at 20 °C for 12 h and then stored at 2 °C for up to 28 days. MeSA reduced CI and enhanced the accumulation of putrescine, spermidine, and spermine, which was associated with increased gene expression levels and activities of arginase, arginine decarboxylase, and ornithine decarboxylase at most sampling times. MeSA also increased nitric oxide synthase activity, which at least partly contributed to the increased nitric oxide content. The results indicate that MeSA activates the different pathways of arginine catabolism in cold-stored fruit and that the reduction in CI by MeSA may be due to the coordinated metabolism of arginine and the increase in polyamines and nitric oxide levels.

L-arginine mediated renaturation enhances yield of human, α6 Type IV collagen non-collagenous domain from bacterial inclusion bodies.

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Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Sudhakar, Yakkanti Akul

2012-10-01

The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated.

The use of nucleosides and arginine as alternative energy sources by coagulase-negative staphylococci in view of meat fermentation.

Science.gov (United States)

Janssens, M; Van der Mijnsbrugge, A; Sánchez Mainar, M; Balzarini, T; De Vuyst, L; Leroy, F

2014-05-01

The ability of coagulase-negative staphylococci (CNS) to use alternative energy sources in meat may partially explain their occurrence in fermented meats. Of 61 CNS strains tested, all metabolized adenosine and inosine in a meat simulation medium (MSM). The ability to catabolize arginine via the arginine deiminase (ADI) pathway varied between strains. All tested strains of Staphylococcus carnosus and Staphylococcus epidermidis possessed an arcA gene and showed ADI activity, whereas other species, such as Staphylococcus equorum and Staphylococcus succinus, did not. Arginine catabolic mobile elements (ACME), as in the positive control S. epidermidis ATCC 12228, were uncommon and only found in Staphylococcus xylosus 3PA6 (sausage isolate) and Staphylococcus chromogenes G222 (teat apex isolate). Monoculture experiments were performed in MSM with S. carnosus 833 and SS3-4, S. xylosus G211, and S. epidermidis ATCC 12228 and 2S7-4. At all pH values tested (5.3, 5.8, and 6.5), the strains of S. carnosus catabolized arginine faster than the strains of S. xylosus and S. epidermidis. Only at pH 6.5 could a low ADI activity be found for S. xylosus G211. Increased ADI activity occurred in the case of the ACME-positive S. epidermidis ATCC 12228, when compared to the ACME-negative S. epidermidis 2S7-4. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antioxidant Activity of Syringic Acid Prevents Oxidative Stress in l-arginine-Induced Acute Pancreatitis: An Experimental Study on Rats.

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Cikman, Oztekin; Soylemez, Omer; Ozkan, Omer Faruk; Kiraz, Hasan Ali; Sayar, Ilyas; Ademoglu, Serkan; Taysi, Seyithan; Karaayvaz, Muammer

2015-05-01

The aim of this study was to investigate the possible protective role of antioxidant treatment with syringic acid (SA) on l-arginine-induced acute pancreatitis (AP) using biochemical and histopathologic approaches. A total of 30 rats were divided into 3 groups. The control group received normal saline intraperitoneally. The AP group was induced by 3.2 g/kg body weight l-arginine intraperitoneally, administered twice with an interval of 1 hour between administrations. The AP plus SA group, after having AP induced by 3.2 g/kg body weight l-arginine, was given SA (50 mg kg(-1)) in 2 parts within 24 hours. The rats were killed, and pancreatic tissue was removed and used in biochemical and histopathologic examinations. Compared with the control group, the mean pancreatic tissue total oxidant status level, oxidative stress index, and lipid hydroperoxide levels were significantly increased in the AP group, being 30.97 ± 7.13 (P < 0.05), 1.76 ± 0.34 (P < 0.0001), and 19.18 ± 4.91 (P < 0.01), respectively. However, mean total antioxidant status and sulfhydryl group levels were significantly decreased in the AP group compared with the control group, being 1.765 ± 0.21 (P < 0.0001) and 0.21 ± 0.04 (P < 0.0001), respectively. SA reduces oxidative stress markers and has antioxidant effects. It also augments antioxidant capacity in l-arginine-induced acute toxicity of pancreas in rats.

THE EFFECT OF L- ARGININE ON OXIDATIVE STRESS AND MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE

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L. P. Martynyuk

2017-07-01

Full Text Available Background. One of the severest complications of diabetes is diabetic kidney disease (DKD. Microalbuminuria (MAU is one of the first signals of DKD and an important pathogenetic mechanism of disease progression. With diabetes dramatically antioxidant properties worsen. Objective. The aim was to investigate the effect of L-arginine on oxidative stress parameters and microalbuminuria in type 2 diabetes mellitus and chronic kidney disease patients. Methods. Total of 57 patients with type 2 diabetes mellitus and chronic kidney disease and 30 healthy subjects (control group were included in the study. The patients were divided into 2 congruent groups. The 1-st group of patients (n=33, in addition to standard therapy, received L-arginine 4.2 g intravenously for 5 days, after that they took it 1,0 g orally three times a day during meals for 1 month. The second group of patients (n=24 received a standard therapy. The concentration of lipid peroxidation products was measured by a spectrophotometric method. The determination of MAU was carried out in morning portion of urine immunological semiquantitative using test strips. Results. Significant improvement in indexes of lipid peroxidation was observed in both groups after therapy (p˂0.01, but in patients treated with L-arginine it was more expressed (p˂0,01. The standard therapy did not significantly affect the level of MAU (p˃0,05. The patients treated with L-Arginine, showed a significant reduction in MAU (p˂0.01. Conclusions. The usage of L-arginine facilitates the correction of lipid peroxidation processes and reduces the severity of microalbuminuria in patients with diabetic kidney disease that slowing its progression.

Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster.

Science.gov (United States)

Wang, Youmei; Lu, Minghua; Tang, Dianping

2018-06-30

A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB 1 -bovine serum albumin (AFB 1 -BSA) conjugate-coated microplate, using arginase-labeled anti-AFB 1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB 1 , and allowed the detection of the analyte at concentrations as low as 3.2 pg mL -1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB 1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff. Copyright © 2018 Elsevier B.V. All rights reserved.

Redox specificity of 2-hydroxyacid-coupled NAD(+/NADH dehydrogenases: a study exploiting "reactive" arginine as a reporter of protein electrostatics.

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Pooja Gupta

Full Text Available With "reactive" arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs and cytoplasmic and mitochondrial malate dehydrogenases (MDHs are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in "reactivity" of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on "reactive" arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of "reactive" arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure or reduce NAD(+ (cationic nicotinamide structure. The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide or reduced (neutral nicotinamide coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme.

N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells.

Science.gov (United States)

Pou, S; Pou, W S; Rosen, G M; el-Fakahany, E E

1991-01-01

This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase. PMID:1671745

Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles

Science.gov (United States)

Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I.; Penna, Mario

2017-01-01

Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens–amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT’s social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT’s many effects on behavior. PMID:28824546

Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles

Directory of Open Access Journals (Sweden)

Walter Wilczynski

2017-08-01

Full Text Available Arginine vasotocin (AVT is the non-mammalian homolog of arginine vasopressin (AVP and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens–amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT’s social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT’s many effects on behavior.

Effect of three different doses of arginine enhanced enteral nutrition on nutritional status and outcomes in well nourished postsurgical cancer patients: a randomized single blinded prospective trial.

Science.gov (United States)

De Luis, D A; Izaola, O; Terroba, M C; Cuellar, L; Ventosa, M; Martin, T

2015-01-01

Patients with head and neck cancer undergoing surgery have a high occurrence of postoperative complications. The aim of our study was to investigate whether postoperative nutrition of head and neck cancer patients, using an enhanced enteral formula with three different doses of arginine could improve nutritional variables as well as clinical outcome, depending of arginine dose. A population of 84 patients with oral and laryngeal cancer was enrolled. At surgery patients were randomly assigned to three different treatment groups, each one containing at less 28 patients. Group I (28 patients) received an enteral diet supplements with a low physiological dose of arginine (5.7 g per day), group II (28 patients) received an isocaloric, isonitrogenous enteral formula with a medium dose of arginine (12.3 g per day) and group III (28 patients) received an isocaloric, isonitrogenous enteral formula with a high dose of arginine (18.9 g per day). The length of postoperative stay had a trend to be better with high dose of arginine received (31.9 ± 17.2 days in group I vs 27.8 ± 15.2 days in group II vs 24.8 ± 18.3 days in group III: p = 0.034). No differences were detected in postoperative infections complications and diarrhea. Fistula was less frequent in groups II and III than I (10.7% group I vs 3.6% group II vs 3.6% group III: p = 0.033), The length of postoperative stay had a trend to be better with high dose of arginine received (31.9 ± 17.2 days in group I vs 27.8 ± 15.2 days in group II vs 24.8 ± 18.3 days in group III: p = 0.034). Our results suggest that these patients could benefit from a high dose of arginine enhanced enteral formula to decrease length of hospital stay and fistula wound complications.

Metabolism of 14C-L-arginine and 14C-L-proline in excised burst buds and stem sections of citrus trees (Citrus unshiu Marc.)

International Nuclear Information System (INIS)

Kato, Tadashi; Yamagata, Makoto; Tsukahara, Sadao

1985-01-01

Arginine and proline, which are the major forms of soluble reserve N, were fed singly in uniformly labelled 14 C-form to excised 2-year-old stem sections with a new shoot, to wood sections, and to burst buds from a 21-year-old satsuma mandarin tree. Metabolism was studied by radioassay and autoradiography. In stem sections with a new shoot, both 14 C-compounds were metabolized to acidic and neutral components, insoluble components, and 14 CO 2 . This conversion occurred to a greater extent in sections fed with arginine than with proline. When 14 C-arginine was fed, the highest 14 C-activity in the cationic fraction of stem sections, bark, wood and new shoots was found in γ-guanidinobutyric acid, followed by γ-aminobutyric acid and proline; low levels of 14 C was also found in ornithine and trace amounts in citrulline. These findings demonstrate that arginine is metabolized by at least two routes: via ornithine and via γ-guanidinobutyric acid. In every organ, the major metabolic products of 14 C-proline were pyrrolidone-5-carboxlic acid, glutamic acid, aspartic acid, asparagine, an unidentified compound (U 5 in Fig. 4), γ-aminobutyric acid and arginine. The basic metabolic pathways in the conversion of Both 14 C-compounds were the same in burst buds, new shoot, bark and wood, although there was a slight difference autoradiographically. (author)

Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine

DEFF Research Database (Denmark)

Orskov, C; Jeppesen, J; Madsbad, S

1991-01-01

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration...... integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed....... In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All...

Microwave heating of arginine yields highly fluorescent nanoparticles

International Nuclear Information System (INIS)

Philippidis, Aggelos; Stefanakis, Dimitrios; Anglos, Demetrios; Ghanotakis, Demetrios

2013-01-01

Brightly fluorescent nanoparticles were produced via a single-step, single-precursor procedure based on microwave heating of an aqueous solution of the amino acid arginine. Key structural and optical properties of the resulting Arg nanoparticles, Arg-dots, are reported and discussed with emphasis on the pH dependence of their fluorescence emission. The surface of the Arg-dots was functionalised through coupling to folic acid, opening up ways for connecting fluorescent nanoparticles to cancer cells. The generality and versatility of the microwave heating procedure was further demonstrated by the synthesis of different types of carbon nanoparticles, such as CE-dots, that were produced by use of citric acid and ethanolamine as precursors and compared to the Arg-dots.

Effect of Hydroxylamine Sulfate on Volumetric Behavior of Glycine, L-Alanine, and L-Arginine in Aqueous Solution

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Jie Chen

2013-01-01

Full Text Available The apparent molar volumes of glycine, L-alanine, and L-arginine in aqueous hydroxylamine sulfate solutions have been determined at T=298.15 K and atmospheric pressure. The standard partial molar volumes, V20, corresponding partial molar volumes of transfer, ΔtrV20, and hydration numbers, NH, have been calculated for these α-amino acids from the experimental data. The ΔtrV20 values are positive for glycine, L-alanine, and L-arginine and are all increased with the increase in the concentration of hydroxylamine ions. These parameters obtained from the volumetric data are interpreted in terms of various mixing effects between amino acids and hydroxylamine sulfate in aqueous solutions.

l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy

DEFF Research Database (Denmark)

Szabo, P; Lantos, J; Nagy, L

2016-01-01

lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range...

Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

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Ewa Sawosz

2015-10-01

Full Text Available Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO and rGO functionalized with arginine (rGO + Arg or proline (rGO + Pro. The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.

Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

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Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Vadalasetty, Krishna Prasad; Grodzik, Marta; Wierzbicki, Mateusz; Kurantowicz, Natalia; Strojny, Barbara; Hotowy, Anna; Lipińska, Ludwika; Jagiełło, Joanna; Chwalibog, André

2015-01-01

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. PMID:26512645

Colostrum and milk production in multiparous sows fed supplementary arginine during gestation and lactation

DEFF Research Database (Denmark)

Larsen, Uffe Krogh; Oksbjerg, Niels; Purup, Stig

2016-01-01

) or isonitrogenous amounts of alanine (CON; n = 10) from d 30 of gestation until weaning on d 28 of lactation (in 2 blocks). Piglets were weighed 0, 12, 24, and 36 h after birth of the first piglet and on d 2, 7, 14, 21, and 28 in lactation for estimation of colostrum and milk intake. Colostrum samples obtained at 0......, 12, 24, and 36 h after parturition and milk from sows on d 3, 10, 17, and 24 of lactation were analyzed for macrochemical composition. Also, the content of IGF-I was determined in colostrum. Arginine supplementation decreased lactose and increased DM content of colostrum (P ... on colostrum or milk yield, piglet weight, piglet ADG, or fat content of colostrum and milk was observed (P > 0.10). Concentration of protein and IGF-I tended to be increased in ARG-fed sows. In conclusion, arginine supplementation of sows during gestation and lactation affected macrochemical composition...

Blockade of the Naloxone-induced Aversion in Morphine-conditioned Wistar Rats by L-Arginine Intra-central Amygdala

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Mahnaz Rahimpour

2011-03-01

Full Text Available AbstractObjective(sSingle injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence.Materials and MethodsConditioning to morphine (2.5-10 mg/kg, s.c. was established in adult male Wistar rats (weighing 200-250 g using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior to naloxone-paired place conditioning testing.ResultsThe results showed that morphine produced a significant dose-dependent place preference in animals. Naloxone (0.1-0.4 mg/kg, i.p. injections pre-testing of the response to morphine (7.5 mg/kg, s.c. caused a significant aversion at the higher doses (0.4 mg/kg, i.p.. This response was reversed by microinjection of L-arginine (0.3-3 µg/rat, intra-central amygdala prior to naloxone on the day of the testing. The response to L-arginine was blocked by pre-injection of NG-nitro-L-arginine methyl ester (L-NAME (intra-central amygdala.ConclusionA single injection of naloxone on the test day of morphine place conditioning may simply reveal the occurrence of morphine dependence in rats, and that the nitric oxide in the central amygdala most likely plays a key role in this phenomenon.

Effect of L-arginine dietary supplementation on salivary urea concentration and pH in physically active individuals.

Science.gov (United States)

Vuletic, L; Spalj, S; Rogic, D; Ruzic, L; Alajbeg, I

2013-12-01

The aim of this study was to assess if the consumption of 3 g of a commercially available L-arginine dietary supplement causes a postabsorptive rise in urea concentration or pH of unstimulated saliva in a group of physically active individuals. Salivary urea and pH were determined for 117 participants in a randomized double-blinded placebo-controlled study. Samples were collected by 'spitting' method in fasting conditions. One hour prior to their second visit, participants consumed three tablets of L-arginine or placebo. Urea concentration was significantly lower at second measurement for both the study and control group. The magnitude of the change was not significant between the groups. pH was higher for both groups at second measurement, but only significant for the study group. The magnitude of the change was significant between the groups. Participants who intermittently ingested protein dietary supplements and those with a Body Mass Index (BMI) higher than 25 had significantly higher basal urea concentration. The results of this study did not confirm the hypothesis. Further studies are needed to determine the effects of different doses of L-arginine supplements on the biochemical composition of saliva and the influence of their long-term consumption on the risk of developing dental diseases. © 2013 Australian Dental Association.

Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

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Takechi-Haraya, Yuki; Saito, Hiroyuki

2018-01-01

Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterization of conserved arginine residues on Cdt1 that affect licensing activity and interaction with Geminin or Mcm complex.

Science.gov (United States)

You, Zhiying; Ode, Koji L; Shindo, Mayumi; Takisawa, Haruhiko; Masai, Hisao

2016-05-02

All organisms ensure once and only once replication during S phase through a process called replication licensing. Cdt1 is a key component and crucial loading factor of Mcm complex, which is a central component for the eukaryotic replicative helicase. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent rereplication. Here, we address the mechanism of DNA licensing using purified Cdt1, Mcm and Geminin proteins in combination with replication in Xenopus egg extracts. We mutagenized the 223th arginine of mouse Cdt1 (mCdt1) to cysteine or serine (R-S or R-C, respectively) and 342nd and 346th arginines constituting an arginine finger-like structure to alanine (RR-AA). The RR-AA mutant of Cdt1 could not only rescue the DNA replication activity in Cdt1-depleted extracts but also its specific activity for DNA replication and licensing was significantly increased compared to the wild-type protein. In contrast, the R223 mutants were partially defective in rescue of DNA replication and licensing. Biochemical analyses of these mutant Cdt1 proteins indicated that the RR-AA mutation disabled its functional interaction with Geminin, while R223 mutations resulted in ablation in interaction with the Mcm2∼7 complex. Intriguingly, the R223 mutants are more susceptible to the phosphorylation-induced inactivation or chromatin dissociation. Our results show that conserved arginine residues play critical roles in interaction with Geminin and Mcm that are crucial for proper conformation of the complexes and its licensing activity.

Functional role of proteolytic cleavage at arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis

International Nuclear Information System (INIS)

Tate, K.M.; Higgins, D.L.; Holmes, W.E.; Winkler, M.E.; Heyneker, H.L.; Vehar, G.A.

1987-01-01

Activation of the zymogen form of a serine protease is associated with a conformational change that follows proteolysis at a specific site. Tissue-type plasminogen activator (t-PA) is homologous to mammalian serine proteases and contains an apparent activation cleavage site at arginine-275. To clarify the functional consequences of cleavage at arginine-275 of t-PA, site-specific mutagenesis was performed to convert arginine-275 to a glutamic acid. The mutant enzyme (designated Arg-275 → Glu t-PA) could be converted to the two-chain form by Staphylococcus aureus V8 protease but not by plasmin. The one-chain form was 8 times less active against the tripeptide substrate H-D-isoleucyl-L-prolyl-L-arginine-rho-nitroanilide (S-2288), and the ability of the enzyme to activate plasminogen in the absence of fibrinogen was reduced 20-50 times compared to the two-chain form. In contrast, one-chain Arg-275 → Glu t-PA has equal activity to the two-chain form when assayed in the presence of physiological levels of fibrinogen and plasminogen. Fibrin bound significantly more of the one-chain form of t-PA than the two-chain form for both the wild-type and mutated enzymes. One- and two-chain forms of the wild-type and mutated plasminogen activators slowly formed complexes with plasma protease inhibitors, although the one-chain forms showed decreased complex formation with → 2 -macroglobulin. The one-chain form of t-PA therefore is fully functional under physiologic conditions and has a increased fibrin binding compared to the two-chain form

Modeling of Reactive Blue 19 azo dye removal from colored textile wastewater using L-arginine-functionalized Fe{sub 3}O{sub 4} nanoparticles: Optimization, reusability, kinetic and equilibrium studies

Energy Technology Data Exchange (ETDEWEB)

Dalvand, Arash; Nabizadeh, Ramin [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Reza Ganjali, Mohammad [Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Khoobi, Mehdi [Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176 (Iran, Islamic Republic of); Nazmara, Shahrokh [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Hossein Mahvi, Amir, E-mail: ahmahvi@yahoo.com [Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Center for Solid Waste Research, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); National Institute of Health Research, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-04-15

This study aimed to investigate the removal of Reactive Blue 19 from colored wastewater using Fe{sub 3}O{sub 4} magnetic nanoparticles modified with L-arginine (Fe{sub 3}O{sub 4}@L-arginine). In order to investigate the effect of independent variables on dye removal and determining the optimum condition, the Box–Behnken Design (BBD) under Response Surface Methodology (RSM) was employed. Fe{sub 3}O{sub 4}@L-arginine nanoparticles were synthesized and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and vibrating sample magnetometer. Applying Fe{sub 3}O{sub 4}@L-arginine nanoparticles for dye removal showed that; by increasing adsorbent dose and decreasing pH, dye concentration, and ionic strength dye removal has been increased. In the optimum condition, Fe{sub 3}O{sub 4}@L-arginine nanoparticles were able to remove dye as high as 96.34% at an initial dye concentration of 50 mg/L, adsorbent dose of 0.74 g/L, and pH 3. The findings indicated that dye removal followed pseudo-second-order kinetic (R{sup 2}=0.999) and Freundlich isotherm (R{sup 2}=0.989). Based on the obtained results, as an efficient and reusable adsorbent, Fe{sub 3}O{sub 4}@L-arginine nanoparticles can be successfully applied for dye removal from colored wastewater. - Highlights: • The Fe{sub 3}O{sub 4}@L-arginine removed RB 19 azo dye from wastewater efficiently. • BBD under RSM was used to analyze and optimize the adsorption process. • pH was the most influential parameter in dye removal.

Functional and molecular effects of arginine butyrate and prednisone on muscle and heart in the mdx mouse model of Duchenne Muscular Dystrophy.

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Alfredo D Guerron

2010-06-01

Full Text Available The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin.In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy.These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity.

Functional and molecular effects of arginine butyrate and prednisone on muscle and heart in the mdx mouse model of Duchenne Muscular Dystrophy.

Science.gov (United States)

Guerron, Alfredo D; Rawat, Rashmi; Sali, Arpana; Spurney, Christopher F; Pistilli, Emidio; Cha, Hee-Jae; Pandey, Gouri S; Gernapudi, Ramkishore; Francia, Dwight; Farajian, Viken; Escolar, Diana M; Bossi, Laura; Becker, Magali; Zerr, Patricia; de la Porte, Sabine; Gordish-Dressman, Heather; Partridge, Terence; Hoffman, Eric P; Nagaraju, Kanneboyina

2010-06-21

The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD) is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin. In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated) mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy. These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity.

Redox Specificity of 2-Hydroxyacid-Coupled NAD+/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics

Science.gov (United States)

Durani, Susheel

2013-01-01

With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD+-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD+ (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. PMID:24391777

Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502.

Science.gov (United States)

Fredrick, Chase M; Lin, Guangyun; Johnson, Eric A

2017-07-01

Botulinum neurotoxin (BoNT), produced by neurotoxigenic clostridia, is the most potent biological toxin known and the causative agent of the paralytic disease botulism. The nutritional, environmental, and genetic regulation of BoNT synthesis, activation, stability, and toxin complex (TC) formation is not well studied. Previous studies indicated that growth and BoNT formation were affected by arginine and glucose in Clostridium botulinum types A and B. In the present study, C. botulinum ATCC 3502 was grown in toxin production medium (TPM) with different levels of arginine and glucose and of three products of arginine metabolism, citrulline, proline, and ornithine. Cultures were analyzed for growth (optical density at 600 nm [OD 600 ]), spore formation, and BoNT and TC formation by Western blotting and immunoprecipitation and for BoNT activity by mouse bioassay. A high level of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold, enhanced growth, slowed lysis, and reduced endospore production by greater than 1,000-fold. Similar effects on toxin production were seen with equivalent levels of citrulline but not ornithine or proline. In TPM lacking glucose, levels of formation of BoNT/A1 and TC were significantly decreased, and extracellular BoNT and TC proteins were partially inactivated after the first day of culture. An understanding of the regulation of C. botulinum growth and BoNT and TC formation should be valuable in defining requirements for BoNT formation in foods and clinical samples, improving the quality of BoNT for pharmaceutical preparations, and elucidating the biological functions of BoNTs for the bacterium. IMPORTANCE Botulinum neurotoxin (BoNT) is a major food safety and bioterrorism concern and is also an important pharmaceutical, and yet the regulation of its synthesis, activation, and stability in culture media, foods, and clinical samples is not well understood. This paper provides insights into the effects of critical

Arginine and vitamin E improve the immune response after a Salmonella challenge in broiler chicks

Science.gov (United States)

Two experiments were conducted to evaluate the effects of arginine (ARG), vitamin E (VE), and mannanoligosaccharide (MOS) on the immune response and clearance of Salmonella in broiler chickens. In each experiment, chicks were randomly distributed into 4 groups: antibiotic-free diet (negative contro...

[L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

Science.gov (United States)

Kopyl'chuk, G P; Buchkovskaia, I M

2014-01-01

The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

Mutation of exposed hydrophobic amino acids to arginine to increase protein stability

OpenAIRE

Strub, Caroline; Alies, Carole; Lougarre, Andrée; Ladurantie, Caroline; Czaplicki, Jerzy; Fournier, Didier

2004-01-01

Abstract Background One strategy to increase the stability of proteins is to reduce the area of water-accessible hydrophobic surface. Results In order to test it, we replaced 14 solvent-exposed hydrophobic residues of acetylcholinesterase by arginine. The stabilities of the resulting proteins were tested using denaturation by high temperature, organic solvents, urea and by proteolytic digestion. Conclusion Altough the mutational effects were rather small, this strategy proved to be successful...

Amiloride-enhanced gene transfection of octa-arginine functionalized calcium phosphate nanoparticles.

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Juan Ramón Vanegas Sáenz

Full Text Available Nanoparticles represent promising gene delivery systems in biomedicine to facilitate prolonged gene expression with low toxicity compared to viral vectors. Specifically, nanoparticles of calcium phosphate (nCaP, the main inorganic component of human bone, exhibit high biocompatibility and good biodegradability and have been reported to have high affinity for protein or DNA, having thus been used as gene transfer vectors. On the other hand, Octa-arginine (R8, which has a high permeability to cell membrane, has been reported to improve intracellular delivery systems. Here, we present an optimized method for nCaP-mediated gene delivery using an octa-arginine (R8-functionalized nCaP vector containing a marker or functional gene construct. nCaP particle size was between 220-580 nm in diameter and all R8-functionalized nCaPs carried a positive charge. R8 concentration significantly improved nCaP transfection efficiency with high cell compatibility in human mesenchymal stem cells (hMSC and human osteoblasts (hOB in particular, suggesting nCaPs as a good option for non-viral vector gene delivery. Furthermore, pre-treatment with different endocytosis inhibitors identified that the endocytic pathway differed among cell lines and functionalized nanoparticles, with amiloride increasing transfection efficiency of R8-functionalized nCaPs in hMSC and hOB.

Effects of simvastatin on CAT-1-mediated arginine transport and NO level under high glucose conditions in conditionally immortalized rat inner blood-retinal barrier cell lines (TR-iBRB).

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Tun, Temdara; Kang, Young-Sook

2017-05-01

Hyperglycemia causes the breakdown of the blood-retinal barrier by impairing endothelial nitric oxide synthase (eNOS) function. Statins have many pleiotropic effects such as improving endothelial barrier permeability and increasing eNOS mRNA stability. The objective of this study was to determine effect of simvastatin on l-arginine transport and NO production under high-glucose conditions in conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB). Changes in l-arginine transport uptake and, expression levels of cationic amino acid transporter 1 (CAT-1) and eNOS mRNA were investigated after pre-treatment with simvastatin and NOS inhibitors (l-NMMA and l-NAME) under high-glucose conditions using TR-iBRB, an in vitro model of iBRB. The NO level released from TR-iBRB cells was examined using Griess reagents. Under high glucose conditions, [ 3 H]l-arginine uptake was decreased in TR-iBRB cells. Simvastatin pretreatment elevated [ 3 H]l-arginine uptake, the expression levels of CAT-1 and eNOS mRNA, and NO production under high-glucose conditions. Moreover, the co-treatment with simvastatin and NOS inhibitors reduced [ 3 H]l-arginine uptake compared to pretreatment with simvastatin alone. Our results suggest that, in the presence of high-glucose levels, increased l-arginine uptake due to simvastatin treatment was associated with increased CAT-1 and eNOS mRNA levels, leading to higher NO production in TR-iBRB cells. Thus, simvastatin might be a good modulator for diabetic retinopathy therapy by increasing of the l-arginine uptake and improving endothelial function in retinal capillary endothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of four arginine kinases in the ciliate Paramecium tetraurelia: Investigation on the substrate inhibition mechanism.

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Yano, Daichi; Suzuki, Takaya; Hirokawa, Saki; Fuke, Kyoko; Suzuki, Tomohiko

2017-08-01

The ciliate Paramecium tetraurelia contains four arginine kinase genes (AK1-4). We detected cDNA for only three of the AKs (AK1-3) via PCR. Recombinant AK1-4 were expressed in Escherichia coli and their kinetics parameters determined. AK3 showed typical substrate inhibition toward arginine, and enzymatic activity markedly decreased when arginine concentration increased. This is the first example of substrate inhibition in wild-type phosphagen kinases. To explore the substrate inhibition mechanism, site-directed mutations were generated, targeting the amino acid sequence D-D-S-Q-V at positions 77-81 in P. tetraurelia AK3. Among the mutants, substrate inhibition was lost remarkably in the S79A mutant. In spite of high amino acid sequence identity (91%) between P. tetraurelia AK3 and AK4, the enzymatic activity of AK4 was less by 3% than that of AK3. We noticed that the conservative G298 was unusually replaced by R in P. tetraurelia AK4, and we constructed two mutants, R298G/AK4 and G298R/AK3. Enzymatic activity of the former mutant was comparable with that of the wild-type AK3, whereas that of the latter mutant was dramatically reduced. Thus, we concluded that the significantly low activity of P. tetraurelia AK4 is due to the residue R298. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification and characterization of an arginine kinase as a major allergen from silkworm (Bombyx mori) larvae.

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Liu, Zhigang; Xia, Lixin; Wu, Yulan; Xia, Qingyou; Chen, Jiajie; Roux, Kenneth H

2009-01-01

The silkworm, Bombyx mori, is an important insect in the textile industry and its pupa are used in Chinese cuisine and traditional Chinese medicine. The silk, urine and dander of silkworms is often the cause of allergies in sericulture workers and the pupa has been found to be a food allergen in China. Recent studies have focused on reporting cases of silkworm allergies, but only a few studies have addressed the specific allergens present in the B. mori silkworm. We collected sera from 10 patients with a positive skin prick test to silkworm crude extract (SCE) and analyzed these samples by Western blot and ELISA. The cDNA of arginine kinase from the B. mori silkworm was also cloned and expressed in high yield in Escherichia coli. Allergenicity and cross-allergenicity of the recombinant B. mori arginine kinase (rBmAK) were investigated by ELISA inhibition assay. Collected sera all reacted to a 42-kDa protein in a Western blot with SCE as the antigen. Preincubation of sera with rBmAK eliminated the reactivity of the patients' sera to this 42-kDa band. All patient sera also exhibited positive reactivity to SCE in an ELISA assay. BmAK also demonstrated cross-reactivity with a recombinant AK from cockroach. Arginine kinase from the B. mori silkworm is a major allergen and crossreacts with cockroach AK. Copyright 2009 S. Karger AG, Basel.

Molecular cloning and characterization of arginine kinase gene of Toxocara canis

OpenAIRE

Sahu, Shivani; Samanta, S.; Harish, D. R.; Sudhakar, N. R.; Raina, O. K.; Shantaveer, S. B.; Madhu, D. N.; Kumar, Ashok

2013-01-01

Toxocara canis is an important gastrointestinal nematode of dogs and also a causative agent of visceral larva migrans in humans. Arginine kinase (AK) gene is one of the important biomolecule of phosphagen kinase of T. canis which is emerging as an exciting novel diagnostic target in toxocarosis. The present study was carried out to clone and characterize AK gene of T. canis for future utilization as a diagnostic molecule. Total RNA was extracted from intact adult worms and reverse transcripti...

Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

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Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

2016-09-10

The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of in ovo feeding of carbohydrates and arginine on hatchability, body weight, energy metabolism and perinatal growth in duck embryos and neonates.

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Tangara, M; Chen, W; Xu, J; Huang, F R; Peng, J

2010-10-01

1. The objective of this study was to test the hypothesis that in ovo feeding of carbohydrates and arginine into the duck amnion may improve the glycogen store and perinatal growth. At 23 d of incubation, fertile eggs were injected with 1·2 ml of sodium chloride (NaCl), sucrose + maltose (CHO), arginine (Arg) or sucrose + maltose + arginine (CHO + Arg), with controls not injected. Body weight, liver and muscle glycogen levels, and hepatic glucose-6-phosphatase activity were determined at 25 d of incubation, at hatch, and at 3 and 7 d posthatch. 2. At hatch and 7 d of age, the body weights were greater in the in ovo-feeding treatments than the controls. Arg and CHO + Arg significantly enhanced liver glycogen level at hatch compared with controls. CHO and CHO + Arg significantly increased muscle glycogen level at 25 d of incubation over controls. CHO and Arg decreased glucose-6-phosphatase at 25 d of incubation, whereas NaCl and CHO + Arg increased glucose-6-phosphatase at hatch relative to controls. 3. In ovo feeding of carbohydrates and arginine at 23 d of incubation may improve glycogen reserves, which may, in turn, provide the energy needed for perinatal growth.

Diurnal changes in polyamine content, arginine and ornithine decarboxylase, and diamine oxidase in tobacco leaves

Czech Academy of Sciences Publication Activity Database

Gemperlová, Lenka; Nováková, Marie; Vaňková, Radomíra; Eder, Josef; Cvikrová, Milena

2006-01-01

Roč. 57, č. 6 (2006), s. 1413-1421 ISSN 0022-0957 R&D Projects: GA ČR GA206/03/0369 Institutional research plan: CEZ:AV0Z50380511 Keywords : Arginine decarboxylase * diamine oxidase * ornithine decarboxylase Subject RIV: ED - Physiology Impact factor: 3.630, year: 2006

Efficacy of desensitizing products containing 8% arginine and calcium carbonate for hypersensitivity relief in MIH-affected molars: an 8-week clinical study.

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Bekes, Katrin; Heinzelmann, Karolin; Lettner, Stefan; Schaller, Hans-Günter

2017-09-01

The objective of this study was to compare the efficacy in reducing hypersensitivity in molar incisor hypomineralization (MIH)-affected molars immediately and over 8 weeks combining a single in-office application and a homed-based program with desensitizing products containing 8% arginine and calcium carbonate. Nineteen children with at least one MIH-affected molar with hypersensitivity were included. Hypersensitivity was assessed with an evaporative (air) stimulus and a tactile stimulus. Each child received a single in-office treatment with a desensitizing paste containing 8% arginine and calcium carbonate (elmex Sensitive Professional desensitizing paste), followed by 8 weeks of brushing twice daily with a desensitizing toothpaste containing 8% arginine, calcium carbonate with 1450 ppm fluoride (elmex Sensitive Professional toothpaste), using the elmex Sensitive Professional toothbrush. Additionally, the corresponding mouthwash (elmex Sensitive Professional mouthwash) was used. Clinical assessments were made at baseline, immediately after the in-office treatment and after 1, 2, 4 and 8 weeks of brushing twice daily. Fifty-six molars with an air blast hypersensitivity score of 2 or 3 (Schiff Cold Air Sensitivity Scale) were included. Application of the desensitizing paste decreased hypersensitivity significantly immediately and throughout the 8 weeks recalls (p MIH. This is the first study evaluating the desensitizing effect of a desensitizing paste containing 8% arginine and calcium carbonate in patients with MIH.

Effect of l-arginine therapy on plasma NO/sub 2/ and NO/sub 3/ levels, and blood pressure in uremic rabbits

International Nuclear Information System (INIS)

Hanif, M.; Khemomal, A.

2011-01-01

Background: Normal kidney function is regulated by Nitric oxide (NO) and Superoxide (O/sub 2/-) in the body, and consequently controls blood pressure. Nitric Oxide promotes natriuresis and diuresis, and therefore results in reduction of blood pressure. The objective of this study was to determine the effect of L-arginine supplementation on blood pressure, urinary protein, nitrite and nitrate in addition to blood urea, serum creatinine and creatinine clearance in uremic rabbits. Methods: This study was carried out in the Department of Biochemistry Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. A total of 48 rabbits were included in the study. Twenty-four of the rabbits on surgical intervention were prepared as uremic and so became hypertensive as well. Two groups were uremic, one group was given L-arginine and the other was remained untreated. Systolic and diastolic blood pressure was measured on week 0, week 2, week 4, and week 6, while blood and urine was collected on week 0 and week 6. Results: On supplementation with L-arginine to uremic rabbits systolic and diastolic blood pressures were decreased significantly. Nitrite/nitrate and urinary protein were corrected to some extent while blood urea and serum creatinine were unaffected. Conclusion: L-arginine has a beneficial role as blood pressure lowering agent in uremic rabbits. It corrects NO/sub 2/NO/sub 3/ plasma level and proteinuria which is indicator of renal failure. (author)

Effect of psychological stress on the L-arginine-nitric oxide pathway and semen quality

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S. Eskiocak

2006-05-01

Full Text Available It has been reported that mental stress causes abnormality of spermiogram parameters. We investigated the effect of psychological stress on the L-arginine-nitric oxide (NO pathway. Semen samples were collected from 29 healthy fourth semester medical students just before (stress and 3 months after (non-stress the final examinations. Psychological stress was measured by the State Anxiety Inventory questionnaire. After standard semen analysis, arginase activity and NO concentration were measured spectrophotometrically in the seminal plasma. Measurements were made in duplicate. During the stress period, sperm concentration (41.28 ± 3.70 vs 77.62 ± 7.13 x 10(6/mL, rapid progressive motility of spermatozoa (8.79 ± 1.66 vs 20.86 ± 1.63% and seminal plasma arginase activity (0.12 ± 0.01 vs 0.22 ± 0.01 U/mL were significantly lower than in the non-stress situation, whereas seminal plasma NO (17.28 ± 0.56 vs 10.02 ± 0.49 µmol/L was higher compared to the non-stress period (P < 0.001 for all. During stress there was a negative correlation between NO concentration and sperm concentration, the percentage of rapid progressive motility and arginase activity (r = -0.622, P < 0.01; r = -0.425, P < 0.05 and r = -0.445, P < 0.05, respectively. These results indicate that psychological stress causes an increase of NO level and a decrease of arginase activity in the L-arginine-NO pathway. Furthermore, poor sperm quality may be due to excessive production of NO under psychological stress. In the light of these results, we suggest that the arginine-NO pathway, together with arginase and NO synthase, are involved in semen quality under stress conditions.

A cyanase is transcriptionally regulated by arginine and involved in cyanate decomposition in Sordaria macrospora.

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Elleuche, Skander; Pöggeler, Stefanie

2008-11-01

Cyanase degrades toxic cyanate to NH3 and CO2 in a bicarbonate-dependent reaction. High concentrations of cyanate are fairly toxic to organisms. Here, we characterize a eukaryotic cyanase for the first time. We have isolated the cyn1 gene encoding a cyanase from the filamentous ascomycete Sordaria macrospora and functionally characterized the cyn1 product after heterologous expression in Escherichia coli. Site-directed mutagenesis confirmed a predicted catalytic centre of three conserved amino-acids. A Deltacyn1 knockout in S. macrospora was totally devoid of cyanase activity and showed an increased sensitivity to exogenously supplied cyanate in an arginine-depleted medium, defects in ascospore germination, but no other obvious morphological phenotype. By means of real-time PCR we have demonstrated that the transcriptional level of cyn1 is markedly elevated in the presence of cyanate and down-regulated by addition of arginine. The putative functions of cyanase in fungi are discussed.

Arginine-phosphate salt bridges between histones and DNA: Intermolecular actuators that control nucleosome architecture

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Yusufaly, Tahir I.; Li, Yun; Singh, Gautam; Olson, Wilma K.

2014-10-01

Structural bioinformatics and van der Waals density functional theory are combined to investigate the mechanochemical impact of a major class of histone-DNA interactions, namely, the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. Principal component analysis reveals that the configurational fluctuations of the sugar-phosphate backbone display sequence-specific directionality and variability, and clustering of nucleosome crystal structures identifies two major salt-bridge configurations: a monodentate form in which the arginine end-group guanidinium only forms one hydrogen bond with the phosphate, and a bidentate form in which it forms two. Density functional theory calculations highlight that the combination of sequence, denticity, and salt-bridge positioning enables the histones to apply a tunable mechanochemical stress to the DNA via precise and specific activation of backbone deformations. The results suggest that selection for specific placements of van der Waals contacts, with high-precision control of the spatial distribution of intermolecular forces, may serve as an underlying evolutionary design principle for the structure and function of nucleosomes, a conjecture that is corroborated by previous experimental studies.

Clinical effectiveness of exogenous L-arginine in patients with coronary heart disease after community-acquired pneumonia

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T. O. Kulynych

2017-02-01

Full Text Available Coronary heart disease and community acquired pneumonia associated with a higher risk for morbidity and mortality. The optimization of treatment of comorbid pathology by medicines which modify endothelium functional state is important. Aim: to study effect of exogenous L-arginine on clinical course of disease, markers of systemic inflammation and endothelial dysfunction in patients with coronary heart disease (CHD and community-acquired pneumonia (CAP. Materials and methods. 60 patients with CHD and CAP (the median 72.50 years, range 66.00; 75.00 were included into the study. Patients were randomized in 2 groups: first – 30 patients with basic therapy combined with L-arginine; and second – 30 patients with basic therapy. hs-CRP, neopterin, РАРР-А, NT-proBNP were measured by ELISA-TEST before treatment and 1 month after. Clinical course was assessed during 1 year of follow-up. Results. In the first group the hospitalization rate due to CHD and heart failure decompensation was significantly rare. Biomarkers changes in the 1st group were significant: hs-CRP was significantly decreased by 57.14 % (in the 2nd group – by 28.57 %; neopterin – by 36.57 % (in the 2nd group – by 20.91 %; РАРР-А – by 35.71 % (in the 2nd group – by 4.76 %. There was revealed a significant decreasing of NT-proBNP levels in patients receiving L-arginine by comparing with basic therapy: with the I stage of heart failure (HF – by 50.97 % vs 21.82 %, with the II-A stage of HF – by 43.82 % vs 5.61 % (p < 0.05. After 1 month of therapy patients from the 1st group had significantly lower rates of neopterin – by 16.46 %, and NT-proBNP – by 40.92 % in the subgroup of patients with II-A stage of HF (p < 0.05 compared with patients who received only the basic therapy. Conclusions. Combination of exogenous L-arginine and basic therapy in patients with CHD and CAP was associated with benign clinical course and positive changes of endothelium functional

A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

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Kim, Myoung Hyoun; Kim, Seul-Gi; Kim, Dae-Weung

2018-06-15

We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent. Copyright © 2018 John Wiley & Sons, Ltd.

Formation and enzymatic degradation of poly-l-arginine/fucoidan multilayer films.

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Webber, Jessie L; Benbow, Natalie L; Krasowska, Marta; Beattie, David A

2017-11-01

A polyelectrolyte multilayer (PEM) system based on biopolymers has been constructed and studied in its formation and enzymatic breakdown. The multilayer is composed of fucoidan (a proven antimicrobial/anti-inflammatory seaweed-based polysaccharide) and poly-l-arginine (a polypeptide that can be readily degraded with trypsin to yield arginine, a known NO donor), thus making the multilayer a potential dual action surface treatment for wound dressings. Studies on the formation of the multilayer revealed that the film built-up in the expected stepwise manner with consistent reversal of the zeta potential upon the adsorption of each subsequent polyion. The completed film (8 bilayers) was seen to have low hydration (30% water), as determined by H 2 O/D 2 O solvent replacement studies using the quartz crystal microbalance, with an adsorbed mass (without hydration water) of approx. 4.8μgcm -2 , as determined by quantitative attenuated total reflectance Fourier transform infrared (ATR FTIR) spectroscopy. The enzymatic breakdown of the film in response to exposure to trypsin was also investigated, and the film was seen to release both polymers over time, with a projected complete film removal period of approximately 24h. Critically, this information was determined using ATR FTIR spectroscopy experiments, which allowed unambiguous deconvolution of the removal rates of the two polyions, which is information that cannot be obtained from other methodologies used to study enzymatic breakdown of surface films. Copyright © 2017 Elsevier B.V. All rights reserved.

The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.

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Wolff, M S; Schenkel, A B

2018-02-01

Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.

Analysis of L-citrulline and L-arginine in Ficus deltoidea leaf extracts by reverse phase high performance liquid chromatography

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Shafaei, Armaghan; Aisha, Abdalrahim F. A.; Siddiqui, Mohammad Jamshed Ahmad; Ismail, Zhari

2015-01-01

Background: Ficus deltoidea (FD) is one of the native plants widely distributed in several countries in Southeast Asia. Previous studies have shown that FD leaf possess antinociceptive, wound healing and antioxidant properties. These beneficial effects have been attributed to the presence of primary and secondary metabolites such as polyphenols, amino acids and flavonoids. Objective: The aim was to develop a reverse phase high-performance liquid chromatography method with ultraviolet detection that involves precolumn derivatisation with O-phthaladehyde for simultaneous analysis of two amino acids L-citrulline and L-arginine in FD leaf extracts. Materials and Methods: An isocratic elution program consisting of methanol: acetonitrile: Water at 45:45:10 v/v (solvent A) and 0.1 M phosphate buffer pH 7.5 (solvent B) at A: B v/v ratio of 80:20 on Zorbax Eclipse C18 SB-Aq column (250 × 4.6 mm, 5 μm) were used. The flow rate was set at 1 ml/min and detection was carried out at 338 nm with 30 min separation time. Results: Good linearity for L-citrulline and L-arginine was obtained in the range 0.1-1000 μg/ml at R2 ≥ 0.998. The limit of detection and limit of quantification values for both L-citrulline and L-arginine were 1 and 5 μg/ml, respectively. The average of recoveries was in the range 94.94-101.95%, with relative standard deviation (%RSD) less than 3%. Intra- and inter-day precision was in the range 96.36-102.43% with RSD less than 2%. Conclusion: All validation parameters of the developed method indicate the method is reliable and efficient for simultaneous determination of L-citrulline and L-arginine for routine analysis of FD. PMID:25598632

Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

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Philippe Holzmuller

2018-04-01

Full Text Available Mononuclear phagocytes (monocytes, dendritic cells, and macrophages are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the

Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats

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Lauren Izabel Medeiros Couto

2015-08-01

Full Text Available ABSTRACTOBJECTIVE: To evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats. METHODS: Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG, after induction of injuries, the rats were observed for 24 h. In the simulation group (SG and the arginine group (AG respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK, lactic dehydrogenase (LDH, aspartate aminotransferase (AST and C-reactive protein (CRP. The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's tmethods were used and p≤ 0.05 was taken to be statistically significant. RESULTS: In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis. CONCLUSION: Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain.

Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase

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Tripathi, Pratima; Chandra, M

2009-01-01

Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes. PMID:20716909

Oral Administration of L-Arginine in Patients With Angina or Following Myocardial Infarction May Be Protective By Increasing Plasma Superoxide Dismutase and Total Thiols With Reduction in Serum Cholesterol and Xanthine Oxidase

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Pratima Tripathi

2009-01-01

Full Text Available Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA and acute myocardial infarction (MI]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD and increase in the levels of total thiols (T-SH and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO. These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes.

[State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine].

Science.gov (United States)

Kurhaliuk, N M

2001-01-01

In experiments on rats with different resistance to hypoxia are investigated processes of mitochondrial respiration, oxidative phosphorylation and calcium capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha-ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration states under exogenous L-arginine injection, decreasing efficacy of respiration processes (respiration control on Chance and ADP/O) under such substrates oxidation, testify to oxide energy support decreasing and reversing nitric oxide inhibit in such conditions. This will be used as mechanism cell regulation succinate dehydrogenase activity. It has shown that L-arginine injection increase calcium mitochondrial capacity low resistance to hypoxia rats using substrates of oxidation succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of nitric oxide precursor influence on this processes limit NO-synthase inhibitor L-NNA.

l-Arginine grafted alginate hydrogel beads: A novel pH-sensitive system for specific protein delivery

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Mohamed S. Mohy Eldin

2015-05-01

Full Text Available Novel pH-sensitive hydrogels based on l-arginine grafted alginate (Arg-g-Alg hydrogel beads were synthesized and utilized as a new carrier for protein delivery (BSA in specific pH media. l-arginine was grafted onto the polysaccharide backbone of virgin alginate via amine functions. Evidences of grafting of alginate were extracted from FT-IR and thermal analysis, while the morphological structure of Arg-g-Alg hydrogel beads was investigated by SEM photographs. Factors affecting on the grafting process e.g. l-arginine concentration, reaction time, reaction temperature, reaction pH, and crosslinking conditions, have been studied. Whereas, grafting efficiency of each factor was evaluated. Grafting of alginate has improved both thermal and morphological properties of Arg-g-Alg hydrogel beads. The swelling behavior of Arg-g-Alg beads was determined as a function of pH and compared with virgin calcium alginate beads. The cumulative in vitro release profiles of BSA loaded beads were studied at different pHs for simulating the physiological environments of the gastrointestinal tract. The amount of BSA released from neat alginate beads at pH 2 was almost 15% after 5 h, while the Arg-g-Alg beads at the same conditions were clearly higher than 45%, then it increased to 90% at pH 7.2. Accordingly, grafting of alginate has improved its release profile behavior particularly in acidic media. The preliminary results clearly suggested that the Arg-g-Alg hydrogel may be a potential candidate for polymeric carrier for oral delivery of protein or drugs.

Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial.

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Alizadeh, Mohammad; Safaeiyan, Abdolrasoul; Ostadrahimi, Alireza; Estakhri, Rassul; Daneghian, Sevana; Ghaffari, Aida; Gargari, Bahram Pourghassem

2012-01-01

We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 μg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO(x)), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO(x). HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO(x) and TG. Copyright © 2012 S. Karger AG, Basel.

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

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Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

2014-08-15

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

Evolution of the Maillard Reaction in Glutamine or Arginine-Dextrinomaltose Model Systems

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Silvia Pastoriza

2016-12-01

Full Text Available Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o-phtaldialdehyde (OPA, 5-Hydroximethylfurfural (HMF, furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm. The systems were prepared by mixing glutamine or arginine with dextrinomaltose (similar ingredients to those used in special enteral formula, and heated at 100 °C, 120 °C and 140 °C for 0 to 30 min. The recorded changes in the concentration of furanic compounds was only useful for longer heating times of high temperatures, while absorbance and fluorescence measurements were useful in all the assayed conditions. In addition, easiness and sensitivity of absorbance and fluorescence make them useful techniques that could be implemented as indicators for monitoring the manufacture of special enteral formulas. Glucosylisomaltol is a useful indicator to monitor the manufacture of glutamine-enriched enteral formulas.

Evolution of the Maillard Reaction in Glutamine or Arginine-Dextrinomaltose Model Systems.

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Pastoriza, Silvia; Rufián-Henares, José Ángel; García-Villanova, Belén; Guerra-Hernández, Eduardo

2016-12-07

Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o -phtaldialdehyde (OPA), 5-Hydroximethylfurfural (HMF), furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm. The systems were prepared by mixing glutamine or arginine with dextrinomaltose (similar ingredients to those used in special enteral formula), and heated at 100 °C, 120 °C and 140 °C for 0 to 30 min. The recorded changes in the concentration of furanic compounds was only useful for longer heating times of high temperatures, while absorbance and fluorescence measurements were useful in all the assayed conditions. In addition, easiness and sensitivity of absorbance and fluorescence make them useful techniques that could be implemented as indicators for monitoring the manufacture of special enteral formulas. Glucosylisomaltol is a useful indicator to monitor the manufacture of glutamine-enriched enteral formulas.

Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

NARCIS (Netherlands)

de Fost, M.; van Trotsenburg, A. S. P.; van Santen, H. M.; Endert, E.; van den Elzen, C.; Kamsteeg, E. J.; Swaab, D. F.; Fliers, E.

2011-01-01

Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with autosomal

Familial neurohypophyseal diabetes insipidus due to a novel mutation in the arginine vasopressin-neurophysin II gene

NARCIS (Netherlands)

Fost, M. de; Trotsenburg, A.S. van; Santen, H.M. van; Endert, E.; Elzen, C. van den; Kamsteeg, E.J.; Swaab, D.F.; Fliers, E.A.

2011-01-01

BACKGROUND: Familial neurohypophyseal (central) diabetes insipidus (DI) is caused by mutations in the arginine vasopressin-neurophysin II (AVP-NPII) gene. The majority of cases is inherited in an autosomal dominant way. In this study, we present the clinical features of a mother and her son with

Independent inactivation of arginine decarboxylase genes by nonsense and missense mutations led to pseudogene formation in Chlamydia trachomatis serovar L2 and D strains

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Graham David E

2009-07-01

Full Text Available Abstract Background Chlamydia have reduced genomes that reflect their obligately parasitic lifestyle. Despite their different tissue tropisms, chlamydial strains share a large number of common genes and have few recognized pseudogenes, indicating genomic stability. All of the Chlamydiaceae have homologs of the aaxABC gene cluster that encodes a functional arginine:agmatine exchange system in Chlamydia (Chlamydophilapneumoniae. However, Chlamydia trachomatis serovar L2 strains have a nonsense mutation in their aaxB genes, and C. trachomatis serovar A and B strains have frameshift mutations in their aaxC homologs, suggesting that relaxed selection may have enabled the evolution of aax pseudogenes. Biochemical experiments were performed to determine whether the aaxABC genes from C. trachomatis strains were transcribed, and mutagenesis was used to identify nucleotide substitutions that prevent protein maturation and activity. Molecular evolution techniques were applied to determine the relaxation of selection and the scope of aax gene inactivation in the Chlamydiales. Results The aaxABC genes were co-transcribed in C. trachomatis L2/434, during the mid-late stage of cellular infection. However, a stop codon in the aaxB gene from this strain prevented the heterologous production of an active pyruvoyl-dependent arginine decarboxylase. Replacing that ochre codon with its ancestral tryptophan codon rescued the activity of this self-cleaving enzyme. The aaxB gene from C. trachomatis D/UW-3 was heterologously expressed as a proenzyme that failed to cleave and form the catalytic pyruvoyl cofactor. This inactive protein could be rescued by replacing the arginine-115 codon with an ancestral glycine codon. The aaxC gene from the D/UW-3 strain encoded an active arginine:agmatine antiporter protein, while the L2/434 homolog was unexpectedly inactive. Yet the frequencies of nonsynonymous versus synonymous nucleotide substitutions show no signs of relaxed

N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

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Zenawit Girmatsion

Full Text Available BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks and atrial fibrillation (a human arrhythmia. Structure-function relationship of the KCNE1 N-terminus for I(Ks modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA' were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'. Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks. Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex.

Characterization and localization of arginine vasotocin receptors in the brain and kidney of an amphibian

International Nuclear Information System (INIS)

Boyd, S.K.

1987-01-01

Because arginine vasotocin (AVT) activates male sexual behaviors in the rough-skinned newt (Taricha granulosa), quantitative autoradiography with radiolabeled arginine vasopressin ( 3 H-AVP) was used to localize and characterize putative AVT receptors in the brain of this amphibian. Binding of 3 H-AVP to sites within the medial pallium was saturable, specific, reversible, of high affinity and low capacity. These binding sites appear to represent authentic central nervous system receptors for AVT. Furthermore, ligand specificity for the binding sites in this amphibian differs from that reported for AVP binding sites in rat brains. Dense concentrations of specific binding sites were located in the olfactory nerve as it entered the olfactory bulb within the medial pallium, dorsal pallium, and amygdala pars lateralis of the telencephalon, and in the tegmental region of the medulla. Concentrations of binding sites differed significantly among various brain regions. A comparison of male and female newts collected during the breeding season revealed no sexual dimorphism. These areas may represent site(s) of action where AVT elicits sexual behaviors in male T. granulosa

Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

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Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

2011-07-27

Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

Arginine inhibits the malignant transformation induced by interferon-gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo.

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Ren, Wenbo; Li, Yang; Xia, Xiaojing; Guo, Wenfei; Zhai, Taiyu; Jin, Yuting; Che, Yanyi; Gao, Haidi; Duan, Xiumei; Ma, Hongxi; Huang, Tinghao; Huang, Jing; Lei, Liancheng

2018-07-15

Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-γ level than that from patients with benign breast disease, showing IFN-γ may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-γ (nutritionally induced) both in vitro and in vivo, and IFN-γ was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition. Copyright © 2018 Elsevier Inc. All rights reserved.

Oligomeric structure and chaperone-like activity of Drosophila melanogaster mitochondrial small heat shock protein Hsp22 and arginine mutants in the alpha-crystallin domain.

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Dabbaghizadeh, Afrooz; Finet, Stéphanie; Morrow, Genevieve; Moutaoufik, Mohamed Taha; Tanguay, Robert M

2017-07-01

The structure and chaperone function of DmHsp22WT, a small Hsp of Drosophila melanogaster localized within mitochondria were examined. Mutations of conserved arginine mutants within the alpha-crystallin domain (ACD) domain (R105G, R109G, and R110G) were introduced, and their effects on oligomerization and chaperone function were assessed. Arginine to glycine mutations do not induce significant changes in tryptophan fluorescence, and the mutated proteins form oligomers that are of equal or smaller size than the wild-type protein. They all form oligomer with one single peak as determined by size exclusion chromatography. While all mutants demonstrate the same efficiency as the DmHsp22WT in a DTT-induced insulin aggregation assay, all are more efficient chaperones to prevent aggregation of malate dehydrogenase. Arginine mutants of DmHsp22 are efficient chaperones to retard aggregation of CS and Luc. In summary, this study shows that mutations of arginine to glycine in DmHsp22 ACD induce a number of structural changes, some of which differ from those described in mammalian sHsps. Interestingly, only the R110G-DmHsp22 mutant, and not the expected R109G equivalent to human R140-HspB1, R116-HspB4, and R120-HspB5, showed different structural properties compared with the DmHsp22WT.

Arginine deiminase pathway enzymes: evolutionary history in metamonads and other eukaryotes.

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Novák, Lukáš; Zubáčová, Zuzana; Karnkowska, Anna; Kolisko, Martin; Hroudová, Miluše; Stairs, Courtney W; Simpson, Alastair G B; Keeling, Patrick J; Roger, Andrew J; Čepička, Ivan; Hampl, Vladimír

2016-10-06

Multiple prokaryotic lineages use the arginine deiminase (ADI) pathway for anaerobic energy production by arginine degradation. The distribution of this pathway among eukaryotes has been thought to be very limited, with only two specialized groups living in low oxygen environments (Parabasalia and Diplomonadida) known to possess the complete set of all three enzymes. We have performed an extensive survey of available sequence data in order to map the distribution of these enzymes among eukaryotes and to reconstruct their phylogenies. We have found genes for the complete pathway in almost all examined representatives of Metamonada, the anaerobic protist group that includes parabasalids and diplomonads. Phylogenetic analyses indicate the presence of the complete pathway in the last common ancestor of metamonads and heterologous transformation experiments suggest its cytosolic localization in the metamonad ancestor. Outside Metamonada, the complete pathway occurs rarely, nevertheless, it was found in representatives of most major eukaryotic clades. Phylogenetic relationships of complete pathways are consistent with the presence of the Archaea-derived ADI pathway in the last common ancestor of all eukaryotes, although other evolutionary scenarios remain possible. The presence of the incomplete set of enzymes is relatively common among eukaryotes and it may be related to the fact that these enzymes are involved in other cellular processes, such as the ornithine-urea cycle. Single protein phylogenies suggest that the evolutionary history of all three enzymes has been shaped by frequent gene losses and horizontal transfers, which may sometimes be connected with their diverse roles in cellular metabolism.

Development and cytotoxicity of Schiff base derivative as a fluorescence probe for the detection of L-Arginine

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Shang, Xuefang; Li, Jie; Guo, Kerong; Ti, Tongyu; Wang, Tianyun; Zhang, Jinlian

2017-04-01

Inspired from biological counter parts, chemical modification of Schiff base derivatives with function groups may provide a highly efficient method to detect amino acids. Therefore, a fluorescent probe involving Schiff base and hydroxyl group has been designed and prepared, which showed high response and specificity for Arginine (Arg) among normal eighteen standard kinds of amino acids (Alanine, Valine, Leucine, Isoleucine, Methionine, Asparticacid, Glutamicacid, Arginine, Glycine, Serine, Threonine, Asparagine, Phenylalanine, Histidine, Tryptophan, Proline, Lysine, Glutamine, Tyrosine and Cysteine). Furthermore, theoretical investigation further illustrated the possible binding mode in the host-guest interaction and the roles of molecular frontier orbitals in molecular interplay. In addition, the synthesized fluorescent probe exhibited high binding ability for Arg and low cytotoxicity to MCF-7 cells over a concentration range of 0-200 μg mL-1 which can be also used as a biosensor for the Arg detection in vivo.

Arginine and antioxidant supplement on performance in elderly male cyclists: a randomized controlled trial.

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Chen, Steve; Kim, Woosong; Henning, Susanne M; Carpenter, Catherine L; Li, Zhaoping

2010-03-23

Human exercise capacity declines with advancing age. These changes often result in loss of physical fitness and more rapid senescence. Nitric oxide (NO) has been implicated in improvement of exercise capacity through vascular smooth muscle relaxation in both coronary and skeletal muscle arteries, as well as via independent mechanisms. Antioxidants may prevent nitric oxide inactivation by oxygen free radicals. The purpose of this study was to investigate the effects of an L-arginine and antioxidant supplement on exercise performance in elderly male cyclists. This was a two-arm prospectively randomized double-blinded and placebo-controlled trial. Sixteen male cyclists were randomized to receive either a proprietary supplement (Niteworks(R), Herbalife International Inc., Century City, CA) or a placebo powder. Exercise parameters were assessed by maximal incremental exercise testing performed on a stationary cycle ergometer using breath-by-breath analysis at baseline, week one and week three. There was no difference between baseline exercise parameters. In the supplemented group, anaerobic threshold increased by 16.7% (2.38 +/- 0.18 L/min, p < 0.01) at week 1, and the effect was sustained by week 3 with a 14.2% (2.33 +/- 0.44 L/min, p < 0.01). In the control group, there was no change in anaerobic threshold at weeks 1 and 3 compared to baseline (1.88 +/- 0.20 L/min at week 1, and 1.86 +/- 0.21 L/min at week 3). The anaerobic threshold for the supplement groups was significantly higher than that of placebo group at week 1 and week 3. There were no significant changes noted in VO2 max between control and intervention groups at either week 1 or week 3 by comparison to baseline. An arginine and antioxidant-containing supplement increased the anaerobic threshold at both week one and week three in elderly cyclists. No effect on VO2 max was observed. This study indicated a potential role of L-arginine and antioxidant supplementation in improving exercise performance in

Response of arginine vasopressin-enhanced green fluorescent protein fusion gene in the hypothalamus of adjuvant-induced arthritic rats

Czech Academy of Sciences Publication Activity Database

Suzuki, H.; Onaka, T.; Kasai, M.; Kawasaki, M.; Ohnishi, H.; Otsubo, H.; Saito, T.; Hashimoto, H.; Yokoyama, T.; Fujihara, H.; Dayanithi, Govindan; Murphy, D.; Nakamura, T.; Ueta, Y.

2009-01-01

Roč. 21, č. 3 (2009), s. 183-190 ISSN 0953-8194 Institutional research plan: CEZ:AV0Z50390512 Keywords : arginine vasopressin * Corticotrophin-releasing hormone * GFP Subject RIV: FH - Neurology Impact factor: 3.700, year: 2009

FlpS, the FNR-Like Protein of Streptococcus suis Is an Essential, Oxygen-Sensing Activator of the Arginine Deiminase System

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Jörg Willenborg

2016-07-01

Full Text Available Streptococcus (S. suis is a zoonotic pathogen causing septicemia and meningitis in pigs and humans. During infection S. suis must metabolically adapt to extremely diverse environments of the host. CcpA and the FNR family of bacterial transcriptional regulators are important for metabolic gene regulation in various bacteria. The role of CcpA in S. suis is well defined, but the function of the FNR-like protein of S. suis, FlpS, is yet unknown. Transcriptome analyses of wild-type S. suis and a flpS mutant strain suggested that FlpS is involved in the regulation of the central carbon, arginine degradation and nucleotide metabolism. However, isotopologue profiling revealed no substantial changes in the core carbon and amino acid de novo biosynthesis. FlpS was essential for the induction of the arcABC operon of the arginine degrading pathway under aerobic and anaerobic conditions. The arcABC-inducing activity of FlpS could be associated with the level of free oxygen in the culture medium. FlpS was necessary for arcABC-dependent intracellular bacterial survival but redundant in a mice infection model. Based on these results, we propose that the core function of S. suis FlpS is the oxygen-dependent activation of the arginine deiminase system.

Meal Pattern of Male Rats Maintained on Amino Acid Supplemented Diets: The Effect of Tryptophan, Lysine, Arginine, Proline and Threonine

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Raghad Ayaso

2014-07-01

Full Text Available The macronutrient composition of the diet has been shown to affect food intake, with proteins having distinct effects. The present study investigated the effect of diet supplementation with individual amino acids (tryptophan, lysine, arginine, proline and threonine on meal pattern among male rats. Meal pattern and body weight were monitored for two weeks. Proline and threonine had minimal effects on meal pattern, while the most pronounced changes were observed in the tryptophan group. Both tryptophan and lysine decreased overall food intake, which was translated into a reduction in body weight. The reduced food intake of the tryptophan group was associated with an increase in meal size, intermeal intervals (IMI and meal time and a decrease in meal number. The decrease in the food intake of the lysine group was associated with a reduction in both IMI and meal number, and this was accompanied by an increase in meal time. Arginine increased meal number, while decreasing IMI. Proline and threonine had a minimal effect on meal pattern. Lysine seems to increase satiety, and arginine seems to decrease it, while tryptophan seems to increase satiety and decrease satiation. Accordingly, changes in meal patterns are associated with the type of amino acid added to the diet.

The Supplementation of Branched-Chain Amino Acids, Arginine, and Citrulline Improves Endurance Exercise Performance in Two Consecutive Days

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I-Shiung Cheng, Yi-Wen Wang, I-Fan Chen, Gi-Sheng Hsu, Chun-Fang Hsueh, Chen-Kang Chang

2016-09-01

Full Text Available The central nervous system plays a crucial role in fatigue during endurance exercise. Branched-chain amino acids (BCAA could reduce cerebral serotonin synthesis by competing with its precursor tryptophan for crossing the blood brain barrier. Arginine and citrulline could prevent excess hyperammonemia accompanied by BCAA supplementation. This study investigated the combination of BCAA, arginine, and citrulline on endurance performance in two consecutive days. Seven male and three female endurance runners ingested 0.17 g·kg-1 BCAA, 0.05 g·kg-1 arginine and 0.05 g·kg-1 citrulline (AA trial or placebo (PL trial in a randomized cross-over design. Each trial contained a 5000 m time trial on the first day, and a 10000 m time trial on the second day. The AA trial had significantly better performance in 5000 m (AA: 1065.7 ± 33.9 s; PL: 1100.5 ± 40.4 s and 10000 m (AA: 2292.0 ± 211.3 s; PL: 2375.6 ± 244.2 s. The two trials reported similar ratings of perceived exertion. After exercise, the AA trial had significantly lower tryptophan/BCAA ratio, similar NH3, and significantly higher urea concentrations. In conclusion, the supplementation could enhance time-trial performance in two consecutive days in endurance runners, possibly through the inhibition of cerebral serotonin synthesis by BCAA and the prevention of excess hyperammonemia by increased urea genesis.

Dietary supplementation with arginine and glutamic acid modifies growth performance, carcass traits, and meat quality in growing-finishing pigs.

Science.gov (United States)

Hu, C J; Jiang, Q Y; Zhang, T; Yin, Y L; Li, F N; Deng, J P; Wu, G Y; Kong, X F

2017-06-01

Sixty Duroc × Large White × Landrace pigs with an average initial BW of 77.1 ± 1.3 kg were used to investigate the effects of dietary supplementation with arginine and glutamic acid on growth performance, carcass traits, and meat quality in growing-finishing pigs. The animals were randomly assigned to 1 of 5 treatment groups (12 pigs/group, male:female ratio 1:1). The pigs in the control group were fed a basal diet (basal diet group), and those in the experimental groups were fed the basal diet supplemented with 2.05% -alanine (isonitrogenous group), 1.0% -arginine (Arg group), 1% glutamic acid + 1.44% -alanine (Glu group), or 1.0% -arginine + 1.0% glutamic acid (Arg+Glu group). After a 60-d period of supplementation, growth performance, carcass traits, and meat quality were evaluated. The results showed no significant differences ( > 0.05) in growth performance and carcass traits of the pigs in the Arg group relative to the basal diet group; however, the longissimus dorsi (LD) muscle and back fat showed a decrease ( 0.05) on the final BW, phase 2 ADFI, and average daily weight gain in pigs but decreased ( acid composition without affecting growth performance and s.c. fat in pigs, providing a novel strategy to enhance meat quality in growing-finishing pigs.

L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.

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Coburn, Lori A; Horst, Sara N; Allaman, Margaret M; Brown, Caroline T; Williams, Christopher S; Hodges, Mallary E; Druce, Jennifer P; Beaulieu, Dawn B; Schwartz, David A; Wilson, Keith T

2016-08-01

L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus control subjects. In active UC, tissue L-Arg was decreased, whereas L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. Patients with UC exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated L-Arg availability and metabolism in UC.

Sensitive determination of bisphenol A base on arginine functionalized nanocomposite graphene film

International Nuclear Information System (INIS)

Zhang Yan; Wang Letao; Lu Daban; Shi Xuezhao; Wang Chunming; Duan Xiaojuan

2012-01-01

Highlights: ► The water-soluble arginine functionalized graphene was produced successfully by an environment-friendly method. ► Electrochemical behaviors and some kinetic parameters of bisphenol A on the Arg-G/GCE were investigated. ► The proposed sensor showed more outstanding sensitivity properties toward the bisphenol A than the reported sensors. ► The proposed method opened a new simply way to detection of bisphenol A in the environmental protection. - Abstract: Arginine (Arg) functionalized graphene (Arg-G) nanocomposite was produced successfully by an environment-friendly method, and the morphology of the nanocomposite was characterized by transmission electron microscopy (TEM), Raman spectra, etc. Based on Arg-G nanocomposite, an electrochemical sensor was fabricated for sensitive detection of bisphenol A (BPA). The electrochemical behaviors of BPA on Arg-G modified glassy carbon electrode (GCE) were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Experimental parameters, such as the accumulation potential and time, scan rate, and the pH value of buffer solution were optimized. Under the optimized conditions, the oxidation peak current was proportional to BPA concentration in the range between 5.0 nmol/L and 40.0 μmol/L with the correlation coefficient of 0.9986 and the limit of detection of 1.1 nmol/L (S/N = 3). Moreover, the fabricated electrode also exhibited good reproducibility and stability. The proposed sensor was successfully employed to determine BPA in real plastic products and the recoveries were satisfactory.

Intracellular acidification reduces l-arginine transport via system y+L but not via system y+/CATs and nitric oxide synthase activity in human umbilical vein endothelial cells.

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Ramírez, Marco A; Morales, Jorge; Cornejo, Marcelo; Blanco, Elias H; Mancilla-Sierpe, Edgardo; Toledo, Fernando; Beltrán, Ana R; Sobrevia, Luis

2018-04-01

l-Arginine is taken up via the cationic amino acid transporters (system y + /CATs) and system y + L in human umbilical vein endothelial cells (HUVECs). l-Arginine is the substrate for endothelial NO synthase (eNOS) which is activated by intracellular alkalization, but nothing is known regarding modulation of system y + /CATs and system y + L activity, and eNOS activity by the pHi in HUVECs. We studied whether an acidic pHi modulates l-arginine transport and eNOS activity in HUVECs. Cells loaded with a pH-sensitive probe were subjected to 0.1-20 mmol/L NH 4 Cl pulse assay to generate pHi 7.13-6.55. Before pHi started to recover, l-arginine transport (0-20 or 0-1000 μmol/L, 10 s, 37 °C) in the absence or presence of 200 μmol/L N-ethylmaleimide (NEM) (system y + /CATs inhibitor) or 2 mmol/L l-leucine (systemy + L substrate) was measured. Protein abundance for eNOS and serine 1177 or threonine 495 phosphorylated eNOS was determined. The results show that intracellular acidification reduced system y + L but not system y + /CATs mediated l-arginine maximal transport capacity due to reduced maximal velocity. Acidic pHi reduced NO synthesis and eNOS serine 1177 phosphorylation. Thus, system y + L activity is downregulated by an acidic pHi, a phenomenon that may result in reduced NO synthesis in HUVECs. Copyright © 2018 Elsevier B.V. All rights reserved.

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome.

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Lance H Rodan

Full Text Available To study the effects of L-arginine (L-Arg on total body aerobic capacity and muscle metabolism as assessed by (31Phosphorus Magnetic Resonance Spectroscopy ((31P-MRS in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes syndrome.We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR in MTTL1 gene with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.At baseline (no L-Arg, MELAS had lower serum Arg (p = 0.001. On 3(1P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr (p = 0.05, decreased ATP (p = 0.018, and decreased intracellular Mg(2+ (p = 0.0002 when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1 increase in mean % maximum work at anaerobic threshold (AT (2 increase in % maximum heart rate at AT (3 small increase in VO(2peak. On (31P-MRS the following mean trends were noted: (1 A blunted decrease in pH after exercise (less acidosis (2 increase in Pi/PCr ratio (ADP suggesting increased work capacity (3 a faster half time of PCr recovery (marker of mitochondrial activity following 5 minutes of moderate intensity exercise (4 increase in torque.These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study.Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.ClinicalTrials.gov NCT01603446.

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

Science.gov (United States)

Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

2015-01-01

To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

Science.gov (United States)

Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

2016-11-01

Pregnancy is a critical time for fetal programming of hypertension. Nitric oxide deficiency during pregnancy causes hypertension in adult offspring. We examined whether maternal melatonin or N-acetylcysteine therapy can prevent N G -nitro-L-arginine-methyl ester-induced fetal programming of hypertension in adult offspring. Next, we aimed to identify potential gatekeeper pathways that contribute to N G -nitro-L-arginine-methyl ester -induced programmed hypertension using the next generation RNA sequencing technology. Pregnant Sprague-Dawley rats were assigned to 4 groups: control, N G -nitro-L-arginine-methyl ester, N G -nitro-L-arginine-methyl ester +melatonin, and N G -nitro-L-arginine-methyl ester+N-acetylcysteine. Pregnant rats received N G -nitro-L-arginine-methyl ester administration at 60 mg/kg/d subcutaneously during pregnancy alone, with additional 0.01% melatonin in drinking water, or with additional 1% N-acetylcysteine in drinking water during the entire pregnancy and lactation. Male offspring (n=8/group) were killed at 12 weeks of age. N G -nitro-L-arginine-methyl ester exposure during pregnancy induced programmed hypertension in adult male offspring, which was prevented by maternal melatonin or N-acetylcysteine therapy. Protective effects of melatonin and N-acetylcysteine against N G -nitro-L-arginine-methyl ester-induced programmed hypertension were associated with an increase in hydrogen sulfide-generating enzymes and hydrogen sulfide synthesis in the kidneys. Nitric oxide inhibition by N G -nitro-L-arginine-methyl ester in pregnancy caused >2000 renal transcripts to be modified during nephrogenesis stage in 1-day-old offspring kidney. Among them, genes belong to the renin-angiotensin system, and arachidonic acid metabolism pathways were potentially involved in the N G -nitro-L-arginine-methyl ester-induced programmed hypertension. However, melatonin and N-acetylcysteine reprogrammed the renin-angiotensin system and arachidonic acid pathway

Short and long-term soy diet vs. casein protects liver steatosis independent of the arginine content

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Non-alcoholic fatty liver disease (NAFLD), the major cause of abnormal liver function, is often associated with obesity. Arginine (ARG) plays a role in modulating body weight/fat, but there are limited data as to the role that ARG may play in soy protein’s ability to protect from liver steatosis. Th...

Characterization of casein and poly-l-arginine multilayer films

Science.gov (United States)

Szyk-Warszyńska, Lilianna; Kilan, Katarzyna; Socha, Robert P.

2014-06-01

Thin films containing casein appear to be a promising material for coatings used in the medical area to promote biomineralization. alfa- and beta-casein and poly-L-arginine multilayer films were formed by the layer-by layer technique and their thickness and mass were analyzed by ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D). We investigated the effect of the type of casein used for the film formation and of the polyethyleneimine anchoring layer on the thickness and mass of adsorbed films. The analysis of the mass of films during their post-treatment with the solutions of various ionic strength and pH provided the information concerning films stability, while the XPS elemental analysis confirmed binding of calcium ions by the casein embedded in the multilayers.

L-Homoarginine and L-arginine are antagonistically related to blood pressure in an elderly population: the Hoorn study

NARCIS (Netherlands)

van der Zwan, L.P.; Davids, M.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Teerlink, T.

2013-01-01

Objectives: Production of nitric oxide by the vascular endothelium is crucial for the maintenance of vascular tone, an important determinant of blood pressure. L-Arginine and its homolog L-homoarginine are competitive substrates of nitric oxide synthase (NOS), whereas asymmetric dimethylarginine

Dialysis Hypotension : A Role for Inadequate Increase in Arginine Vasopressin Levels? A Systematic Literature Review and Meta-Analysis

NARCIS (Netherlands)

Ettema, Esmee M.; Zittema, Debbie; Kuipers, Johanna; Gansevoort, Ron T.; Vart, Priya; de Jong, Paul E.; Westerhuis, Ralf; Franssen, Casper F. M.

2014-01-01

Background: Intradialytic hypotension is a common complication of hemodialysis (HD). Some studies have suggested that inadequate arginine vasopressin (AVP) increase could play a role in the pathogenesis of intradialytic hypotension. However, AVP levels during HD and its relation to hypotension has

Efeito do lipopolissacarídio bacteriano sobre o esvaziamento gástrico de ratos: avaliação do pré-tratamento com Nw-nitro-L-arginine methyl ester (L-NAME The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using Nw-nitro-L-arginine methyl ester (L-NAME

Directory of Open Access Journals (Sweden)

Edgard Ferro Collares

2006-09-01

Full Text Available RACIONAL: Há evidências de que o óxido nítrico participa do mecanismo de retardo do esvaziamento gástrico determinado pelo lipopolissacarídio bacteriano. OBJETIVO: Avaliar o efeito do pré-tratamento com Nw-nitro-L-arginine methyl ester, um inibidor competitivo das óxido nítrico-sintetases, sobre o fenômeno. MATERIAL E MÉTODOS: Utilizaram-se ratos, Wistar, machos, SPF ("specific-pathogen free", adultos, adaptados às condições do laboratório, que após 24 horas de jejum alimentar foram pré-tratados endovenosamente com veículo (salina ou Nw-nitro-L-arginine methyl ester nas doses de 0,5, 1, 2,5 e 5 mg/kg. No tratamento, administrou-se endovenosamente veículo (salina ou lipopolissacarídio (50 µg/kg. O intervalo entre o pré-tratamento e o tratamento foi de 10 minutos, e entre este e a avaliação do esvaziamento gástrico foi de 60 minutos. O esvaziamento gástrico foi avaliado indiretamente através da determinação da retenção gástrica da solução salina marcada com fenol vermelho 10 minutos após administração por via orogástrica. RESULTADOS: Entre os animais pré-tratados com veículo, o tratamento com lipopolissacarídio determinou elevação significativa da retenção gástrica (média = 57% em relação aos tratados com veículo (38,1%. O pré-tratamento com as diferentes doses de Nw-nitro-L-arginine methyl ester não modificou a retenção gástrica nos animais controles do tratamento. O pré-tratamento com Nw-nitro-L-arginine methyl ester com a dose de 1 mg/kg determinou redução discreta, mas significativa, na retenção gástrica (52% nos animais tratados com lipopolissacarídio, em relação ao observado naqueles com pré-tratamento e tratamento com veículo (35,9%. Nos animais pré-tratados com 2,5 e 5 mg/kg de Nw-nitro-L-arginine methyl ester e tratados com lipopolissacarídio, houve aumento significante da retenção gástrica (74,7% e 80,5%, respectivamente em relação aos seus controles pr

The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products.

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Alessandra Apicella

Full Text Available In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD, which is the active component, is mixed with a propylene glycol alginate (PGA gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications.

The crucial role of L-arginine in macrophage activation: What you need to know about it

Czech Academy of Sciences Publication Activity Database

Pekarová, Michaela; Lojek, Antonín

2015-01-01

Roč. 137, SEP2015 (2015), s. 44-48 ISSN 0024-3205 R&D Projects: GA ČR GP13-40882P; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : L-Arginine * Macrophage s * G-protein-coupled receptor Subject RIV: BO - Biophysics Impact factor: 2.685, year: 2015

Effects of L-arginine immobilization on the anticoagulant activity and hemolytic property of polyethylene terephthalate films

International Nuclear Information System (INIS)

Liu Yun; Yang Yun; Wu Feng

2010-01-01

Surface modification of polyethylene terephthalate (PET) films was performed with L-arginine (L-Arg) to gain an improved anticoagulant surface. The surface chemistry changes of modified films were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The in vitro anticoagulant activities of the surface-modified PET films were evaluated by blood clotting test, hemolytic test, and the measurement of clotting time including plasma recalcification time (PRT), activated partial thromboplastin time (APTT), and prothrombin time (PT). The data of blood coagulation index (BCI) for L-arginine modified PET films (PET-Arg) was larger than that for PET at the same blood-sample contact time. The hemolysis ratio for PET-Arg was less than that for PET and within the accepted standard for biomaterials. The PRT and APTT for PET-Arg were significantly prolonged by 189 s and 25 s, respectively, compared to those for the unmodified PET. All results suggested that the currently described modification method could be a possible candidate to create antithrombogenic PET surfaces which would be useful for further medical applications.

Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

Science.gov (United States)

Bisagno, Verónica; Cadet, Jean Lud

2014-09-01

Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

Analogues of arginine vasopressin (AVP) modified in the N-terminal part of the molecule with N-benzylglycine

Czech Academy of Sciences Publication Activity Database

Jastrzebska, B.; Derdowska, I.; Kunčarová, Pavla; Slaninová, Jiřina; Lammek, B.; Olejniczak, B.; Zabrocki, J.

2002-01-01

Roč. 76, - (2002), s. 823-830 ISSN 0137- 5083 Grant - others:PSCSR(PL) 6PO5F01021; PSCSR(PL) BW8000-5-0171-1 Institutional research plan: CEZ:AV0Z4055905 Keywords : arginine vasopressin (AVP) Subject RIV: CC - Organic Chemistry Impact factor: 0.528, year: 2002

Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: interest of a graded arginine supply.

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Breuillard, Charlotte; Darquy, Sylviane; Curis, Emmanuel; Neveux, Nathalie; Garnier, Jean-Pierre; Cynober, Luc; De Bandt, Jean-Pascal

2012-08-01

Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion. Randomized, controlled experimental study. University research laboratory. Zucker diabetic fatty rats. Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n=7) or with graded arginine supply (1-5 g/kg/day) (GA group, n=7) or a standard enteral nutrition (HP group, n=10). Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-α (G: 5.0±1.1 ng/2×10⁶ cells·hr⁻¹; GA: 3.7±0.8 ng/2×10⁶ cells·hr⁻¹; and HP: 1.7±0.6 ng/2×10⁶ cells·hr⁻¹; p1.1 ng/2×10⁶ cells·hr⁻¹; GA: 5.1±1.0 ng/2×10⁶ cells·hr⁻¹; and HP: 1.0±0.5 nmol/2×10⁶ cells·hr⁻¹; pdiabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill diabetic and obese patients.

Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with Cholecystokinin-8

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Daisuke Yamada

2017-06-01

Full Text Available Information from the peripheral organs is thought to be transmitted to the brain by humoral factors and neurons such as afferent vagal or spinal nerves. The common hepatic branch of the vagus (CHBV is one of the main vagus nerve branches, and consists of heterogeneous neuronal fibers that innervate multiple peripheral organs such as the bile duct, portal vein, paraganglia, and gastroduodenal tract. Although, previous studies suggested that the CHBV has a pivotal role in transmitting information on the status of the liver to the brain, the details of its central projections remain unknown. The purpose of the present study was to investigate the brain regions activated by the CHBV. For this purpose, we injected L-arginine or anorexia-associated peptide cholecystokinin-8 (CCK, which are known to increase CHBV electrical activity, into the portal vein of transgenic Arc-dVenus mice expressing the fluorescent protein Venus under control of the activity-regulated cytoskeleton-associated protein (Arc promotor. The brain slices were prepared from these mice and the number of Venus positive cells in the slices was counted. After that, c-Fos expression in these slices was analyzed by immunohistochemistry using the avidin-biotin-peroxidase complex method. Intraportal administration of L-arginine increased the number of Venus positive or c-Fos positive cells in the insular cortex. This action of L-arginine was not observed in CHBV-vagotomized Arc-dVenus mice. In contrast, intraportal administration of CCK did not increase the number of c-Fos positive or Venus positive cells in the insular cortex. Intraportal CCK induced c-Fos expression in the dorsomedial hypothalamus, while intraportal L-arginine did not. This action of CCK was abolished by CHBV vagotomy. Intraportal L-arginine reduced, while intraportal CCK increased, the number of c-Fos positive cells in the nucleus tractus solitarii in a CHBV-dependent manner. The present results suggest that the CHBV

Radioimmunoassay of arginine vasopressin (AVP) and clinical application

International Nuclear Information System (INIS)

Wagner, H.; Haeberle, M.; Franz, H.E.; Maier, V.

1977-01-01

The low circulating levels of vasopressin required an initial extraction procedure. The extraction method itself presented problems with the specificity and the reproducibility of the extracted hormone from serum. The presented paper describes the developement of a radioimmunoassay without an extraction procedure. The AVP was coupled with rabbit-albumin by gluteraldehyde condensation for the immunization of rabbits. Synthetic AVP was iodinated by the method of GREENWOOD and HUNTER (1963) and purified by the addition of Dowex. The antibody cannot differentiate between lysine- and arginine-, ornithine-, glycerine - vasopressin and oxytocin. 1 - 24 ACTH and gastrin did not crosscreact. Normal subjects were found to have 5.7 +- 4.4/uU/ml after a dehydration period of 12 hours. Subjects suffering from psychogenic polydipsia showed normal levels, however, different forms of stress yielded higher levels in normal subjects. In patients suffering from liver cirrhosis the values normalized when ascites was under control. (orig.) [de

Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells

International Nuclear Information System (INIS)

Wang, Y.-H.; Chen, C.-P.; Chan, M.-H.; Chang, M.; Hou, Y.-W.; Chen, H.-H.; Hsu, H.-R.; Liu, Kevin; Lee, H.-J.

2006-01-01

Plasma membranes of plant or animal cells are generally impermeable to peptides or proteins. Many basic peptides have previously been investigated and covalently cross-linked with cargoes for cellular internalization. In the current study, we demonstrate that arginine-rich intracellular delivery (AID) peptides are able to deliver fluorescent proteins or β-galactosidase enzyme into animal and plant cells, as well as animal tissue. Cellular internalization and transdermal delivery of protein could be mediated by effective and nontoxic AID peptides in a neither fusion protein nor conjugation fashion. Therefore, noncovalent AID peptides may provide a useful strategy to have active proteins function in living cells and tissues in vivo

Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

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Kim, P A; Voskresenskaya, O G; Kamensky, A A

2009-06-01

Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

The arginine methyltransferase Rmt2 is enriched in the nucleus and co-purifies with the nuclear porins Nup49, Nup57 and Nup100

International Nuclear Information System (INIS)

Olsson, Ida; Berrez, Jean-Marc; Leipus, Arunas; Ostlund, Cecilia; Mutvei, Ann

2007-01-01

Arginine methylation is a post-translational modification of proteins implicated in RNA processing, protein compartmentalization, signal transduction, transcriptional regulation and DNA repair. In a screen for proteins associated with the nuclear envelope in the yeast Saccharomyces cerevisiae, we have identified the arginine methyltransferase Rmt2, previously shown to methylate the ribosomal protein L12. By indirect immunofluorescence and subcellular fractionations we demonstrate here that Rmt2 has nuclear and cytoplasmic localizations. Biochemical analysis of a fraction enriched in nuclei reveals that nuclear Rmt2 is resistant to extractions with salt and detergent, indicating an association with structural components. This was supported by affinity purification experiments with TAP-tagged Rmt2. Rmt2 was found to co-purify with the nucleoporins Nup49, Nup57 and Nup100, revealing a novel link between arginine methyltransferases and the nuclear pore complex. In addition, a genome-wide transcription study of the rmt2Δ mutant shows significant downregulation of the transcription of MYO1, encoding the Type II myosin heavy chain required for cytokinesis and cell separation

Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

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Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

2014-10-16

Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis--a randomised trial

DEFF Research Database (Denmark)

Schön, T; Idh, J; Westman, A

2011-01-01

In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from...

A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

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Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R

2016-01-01

Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome...... of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin...

Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level

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Viktoriia Tsuber

2017-07-01

Full Text Available Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78 in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53.

Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

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Chang R

2015-05-01

Full Text Available Run Chang,1 Linlin Sun,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective

The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells

International Nuclear Information System (INIS)

Sessa, W.C.; Hecker, M.; Mitchell, J.A.; Vane, J.R.

1990-01-01

The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and N G -monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[ 14 C]Cit to L-[ 14 C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor

Effects of L- Arginine Supplementation on Antioxidant Status and Body Composition in Obese Patients with Pre-diabetes: A Randomized Controlled Clinical Trial

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Siavash Fazelian

2014-10-01

Full Text Available Purpose: The aim of present study was to determine effects of L-Arginine supplementation on antioxidant status and body composition in obese patients with prediabetes. Methods: A double-blind randomized control trial was performed on 46 (24 men, 22 women obese patients with prediabetes. They were divided randomly into two groups. Patients in intervention (n = 23 and control group (n=23 received 3 gr/day L-arginine and placebo, respectively for 8 weeks. Anthropometric indices, dietary intake and biochemical measurements ((serum total antioxidant capacity (TAC, Glutathione Peroxidase (GPx and Superoxide Dismutase (SOD were performed at the baseline and after 8-week intervention. Results: The mean age and BMI of participants were 44.29±8.65 years old and 28.14±1.35 kg/m2, respectively. At the end of study, in both intervention and control group, percentage of carbohydrate decreased and %fat intake increased compared to the baseline (P0.05. Among measured biochemical factors, only serum TAC level showed significant differences at the end of study in the intervention group compared to the control group (pv<0.01. Conclusion: 3gr/day L-Arginine supplementation increased TAC level in obese patients with prediabetes.

Impaired endothelial function after aneurysmal subarachnoid haemorrhage correlates with arginine:asymmetric dimethylarginine ratio

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Bergström, A; Staalsø, J M; Romner, B

2014-01-01

BACKGROUND: Endothelial dysfunction might be involved in the development of cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). METHODS: This prospective observational study of 48 SAH subjects and 23 control subjects examined associations between reactive hyperaemia index (RHI....... Five consecutive measurements were obtained at days 0-2, 3-5, 6-8, 9-11, and 12-15. RESULTS: RHI was 1.67 (0.46) at days 0-2 after SAH but increased at days 3-15 to the same levels as in controls (P... and arginine:ADMA ratio (r=0.43, P

Oral Supplementation with Beta-Hydroxy-Beta-Methylbutyrate, Arginine, and Glutamine Improves Lean Body Mass in Healthy Older Adults.

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Ellis, Amy C; Hunter, Gary R; Goss, Amy M; Gower, Barbara A

2018-04-19

Oral intake of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine may ameliorate muscle loss by stimulating protein synthesis and decreasing protein degradation while simultaneously decreasing inflammation. Previous studies provide evidence for improvement in body composition with dietary supplementation of these ingredients among patients with muscle-wasting diseases. The objectives of this study were to examine the effects of this amino acid mixture on lean body mass, muscle volume, and physical function among healthy older adults. Thirty-one community-dwelling men and women, aged 65-89 years, were randomized to either two oral doses of the amino acid supplement (totaling 3 g HMB, 14 g arginine, 14 g glutamine) or placebo daily for six months. At baseline and month six, lean body mass was measured by air displacement plethysmography, dual-energy X-ray absorptiometry (DXA), and four-compartment model. Muscle volume of quadriceps was quantified by magnetic resonance imaging (MRI), and participants performed a battery of tests to assess physical function. As compared to the placebo group, the treatment group exhibited improvement in a timed stair climb (p =.016) as well as significant increases in lean body mass by all methods of assessment (p lean mass in the supplement group only (p =.035). However, no change was observed in MRI-derived quadriceps volume. Dietary supplementation with HMB, arginine, and glutamine improved total body lean mass among a small sample of healthy older adults. Further research is indicated to elucidate mechanisms of action and to determine whether supplementation may benefit frail elders. Registered under ClinicalTrials.gov identifier no. NCT01057082.

Effects of carbohydrate, branched-chain amino acids, and arginine in recovery period on the subsequent performance in wrestlers

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Jang Tsong-Rong

2011-11-01

Full Text Available Abstract Many athletes need to participate in multiple events in a single day. The efficient post-exercise glycogen recovery may be critical for the performance in subsequent exercise. This study examined whether post-exercise carbohydrate supplementation could restore the performance in the subsequent simulated wrestling match. The effect of branched-chain amino acids and arginine on glucose disposal and performance was also investigated. Nine well-trained male wrestlers participated in 3 trials in a random order. Each trial contained 3 matches with a 1-hr rest between match 1 and 2, and a 2-hr rest between match 2 and 3. Each match contained 3 exercise periods interspersed with 1-min rests. The subjects alternated 10-s all-out sprints and 20-s rests in each exercise period. At the end of match 2, 3 different supplementations were consumed: 1.2 g/kg glucose (CHO trial, 1 g/kg glucose + 0.1 g/kg Arg + 0.1 g/kg BCAA (CHO+AA trial, or water (placebo trial. The peak and average power in the 3 matches was similar in the 3 trials. After the supplementation, CHO and CHO+AA trial showed significantly higher glucose and insulin, and lower glycerol and non-esterified fatty acid concentrations than the placebo trial. There was no significant difference in these biochemical parameters between the CHO and CHO+AA trials. Supplementation of carbohydrate with or without BCAA and arginine during the post-match period had no effect on the performance in the following simulated match in wrestlers. In addition, BCAA and arginine did not provide additional insulinemic effect.

Effects of L-arginine oral supplements in pregnant spontaneously hypertensive rats Efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensas

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José Ricardo Sousa Ayres de Moura

2006-08-01

Full Text Available PURPOSE: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR. METHODS: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1. Pregnancy was confirmed by sperm-positive vaginal smear (Day 0. Wistar-EPM-1 rats served as counterpart control (C-1. SHR rats were randomized in 4 groups (n=10: Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days. Blood pressure was measured by tailcuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean ± SD (Standard Deviation. One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate was used for group comparisons. Statistical significance was accepted as pOBJETIVO: Avaliar os efeitos da oferta oral de L-arginina em ratas prenhas espontaneamente hipertensivas (SHR. MÉTODOS: 30 SHR e 10 Wistar-EPM-1 ratas virgens foram utilizadas no estudo. Antes da distribuição, as fêmeas foram acasaladas com machos da mesma linhagem (3:1; a prenhez foi confirmada pela presença de espermatozóides no esfregaço vaginal. As ratas Wistar-EPM-1 foram utilizadas como controles. As ratas SHR foram aleatoriamente distribuídas em 4 grupos (n=10: Grupo Controle-2, não-tratado; Grupo L-Arginina, tratado com L-arginina; Grupo Alfa-metildopa, tratado com alfa-metildopa; Grupo L-Arginina+Alfa-metildopa, tratado com arginina+Alfa-metildopa. L-arginina (2% foi oferecida ad libitum na água de beber e a Alfa-metildopa (33 mg/Kg foi administrada por gavagem, duas vezes ao dia, durante toda a

In vivo arginine production and nitric oxide synthesis in pregnant Indian women with normal and low body mass indices

Science.gov (United States)

Nitric oxide (NO) has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may be a contributor to pregnancy-induced hypertension or preeclampsia. Because maternal weight is associated with blood pressure...

Assessment of primary eye and skin irritants by in vitro cytotoxicity and phototoxicity models: an in vitro approach of new arginine-based surfactant-induced irritation

International Nuclear Information System (INIS)

Benavides, T.; Mitjans, M.; Martinez, V.; Clapes, P.; Infante, M.R.; Clothier, R.H.; Vinardell, M.P.

2004-01-01

Extensive efforts have been made, recently, to find surfactants with lower irritation potential than those presently commercially available, for use in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of a novel family of dicationic arginine-diglyceride surfactant compounds, 1,2-diacyl,3-O-(L-arginyl)-rac-glycerol with alkyl chain lengths in the range from 8 to 14 carbon atoms, were compared to three commercial surfactants. The end-points used to assess toxicity were the red blood cell lysis assay and uptake of the vital dye neutral red 24 h after dosing (NRU), respectively. Two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, were used as in vitro models to predict the potential phototoxicity which could result in irritation, determined by resazurin reduction to resorufin and neutral red uptake (NRU). All tested surfactants had cytotoxicity effects as demonstrated by and decrease of NR uptake, which showed a clear concentration-response relationship. Concentrations resulting in 50% inhibition of NR uptake (IC 50 ) range from 1 μmol l -1 (hexadecyl trimethyl ammonium bromide) to 565 μmol l -1 (12,12-L-arginine). Erythrocyte haemolysis also showed a clear concentration-response relationship, the 50% of haemolysis ranged from 37 μmol l -1 (10,10-L-arginine) to 151 μmol l -1 (sodium lauryl sulphate). Phototoxicity was performed with 12,12-L-acetyl-arginine, the most stable chemical structure. The validated 3T3 NRU photoxicity assay was used and revealed a phototoxic potential

Arginine substitution of a cysteine in transmembrane helix M8 converts Na+,K+-ATPase to an electroneutral pump similar to H+,K+-ATPase.

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Holm, Rikke; Khandelwal, Jaanki; Einholm, Anja P; Andersen, Jens P; Artigas, Pablo; Vilsen, Bente

2017-01-10

Na + ,K + -ATPase and H + ,K + -ATPase are electrogenic and nonelectrogenic ion pumps, respectively. The underlying structural basis for this difference has not been established, and it has not been revealed how the H + ,K + -ATPase avoids binding of Na + at the site corresponding to the Na + -specific site of the Na + ,K + -ATPase (site III). In this study, we addressed these questions by using site-directed mutagenesis in combination with enzymatic, transport, and electrophysiological functional measurements. Replacement of the cysteine C932 in transmembrane helix M8 of Na + ,K + -ATPase with arginine, present in the H + ,K + -ATPase at the corresponding position, converted the normal 3Na + :2K + :1ATP stoichiometry of the Na + ,K + -ATPase to electroneutral 2Na + :2K + :1ATP stoichiometry similar to the electroneutral transport mode of the H + ,K + -ATPase. The electroneutral C932R mutant of the Na + ,K + -ATPase retained a wild-type-like enzyme turnover rate for ATP hydrolysis and rate of cellular K + uptake. Only a relatively minor reduction of apparent Na + affinity for activation of phosphorylation from ATP was observed for C932R, whereas replacement of C932 with leucine or phenylalanine, the latter of a size comparable to arginine, led to spectacular reductions of apparent Na + affinity without changing the electrogenicity. From these results, in combination with structural considerations, it appears that the guanidine + group of the M8 arginine replaces Na + at the third site, thus preventing Na + binding there, although allowing Na + to bind at the two other sites and become transported. Hence, in the H + ,K + -ATPase, the ability of the M8 arginine to donate an internal cation binding at the third site is decisive for the electroneutral transport mode of this pump.

Effects of acute and chronic stress on the L-arginine nitric oxide pathway in black and white South Africans: the sympathetic activity and ambulatory blood pressure in Africans study.

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Reimann, Manja; Hamer, Mark; Malan, Nicolaas T; Schlaich, Markus P; Lambert, Gavin W; Ziemssen, Tjalf; Boeger, Rainer H; Malan, Leoné

2013-10-01

This study investigated the impact of stress on effectors of the L-arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric dimethylarginine (ADMA). Black (n = 168) and white (n = 206) South African teachers were exposed to a mental and a physical stressor for 1 minute, respectively. Serum samples for determination of l-arginine, NO metabolites, ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during stress exposure. Perception of task stressfulness was assessed on a 7-point Likert scale, and psychological distress was estimated by the General Health Questionnaire. Black South Africans exhibited higher resting levels of NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus 3.9 [1.1] μmol/l, p stress were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74 [1.25] μmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus 0.02 [0.01] μmol/l, p = .004). Ethnicity-by-psychological distress interaction for stress responses was found for l-arginine/ADMA ratio (p = .027). The l-arginine/NO system is affected by psychosocial distress with higher susceptibility in black South Africans. This interaction may contribute to the higher cardiovascular disease risk in black South Africans.

The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution fixes the conformation of the C-terminal peptide

DEFF Research Database (Denmark)

Charrel-Dennis, Marie; Terrazzini, Nadia; McBride, Jeffrey D

2005-01-01

Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross...

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

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C.H. Santuzzi

2015-01-01

Full Text Available Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK and L-arginine treatment both alone and in combination on blood pressure (BP, and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C hypertension, 2K1C+ALSK (ALSK, 2K1C+L-arginine (L-arg, and 2K1C+ALSK+L-arginine (ALSK+L-arg treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

The free energy barrier for arginine gating charge translation is altered by mutations in the voltage sensor domain.

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Christine S Schwaiger

Full Text Available The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure and the first intermediate state towards channel closing (C1, modeled from experimental constraints. We show that conformations within 3 Å of the X-ray structure are obtained in simulations starting from the C1 model, and directly observe the previously suggested sliding 3(10-helix region in S4. Through systematic free energy calculations, we show that the C1 state is a stable intermediate conformation and determine free energy profiles for moving between the states without constraints. Mutations indicate several residues in a narrow hydrophobic band in the voltage sensor contribute to the barrier between the open and C1 states, with F233 in the S2 helix having the largest influence. Substitution for smaller amino acids reduces the transition cost, while introduction of a larger ring increases it, largely confirming experimental activation shift results. There is a systematic correlation between the local aromatic ring rotation, the arginine barrier crossing, and the corresponding relative free energy. In particular, it appears to be more advantageous for the F233 side chain to rotate towards the extracellular side when arginines cross the hydrophobic region.

Expression, purification, crystallization and preliminary crystallographic study of isolated modules of the mouse coactivator-associated arginine methyltransferase 1

Energy Technology Data Exchange (ETDEWEB)

Troffer-Charlier, Nathalie; Cura, Vincent; Hassenboehler, Pierre; Moras, Dino; Cavarelli, Jean, E-mail: cava@igbmc.u-strasbg.fr [IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Département de Biologie et Génomique Structurales, 1 Rue Laurent Fries, Illkirch, F-67404 (France); INSERM, U596, Illkirch, F-67400 (France); CNRS, UMR7104, Illkirch, F-67400 (France); Université Louis Pasteur, Faculté des Sciences de la Vie, Strasbourg, F-67000 (France)

2007-04-01

Isolated modules of mouse coactivator-associated arginine methyltransferase 1 encompassing the protein arginine N-methyltransferase catalytic domain have been overexpressed, purified and crystallized. X-ray diffraction data have been collected and have enabled determination of the structures by multiple isomorphous replacement using anomalous scattering. Coactivator-associated arginine methyltransferase 1 (CARM1) plays a crucial role in gene expression as a coactivator of several nuclear hormone receptors and also of non-nuclear receptor systems. Its recruitment by the transcriptional machinery induces protein methylation, leading to chromatin remodelling and gene activation. CARM1{sub 28–507} and two structural states of CARM1{sub 140–480} were expressed, purified and crystallized. Crystals of CARM1{sub 28–507} belong to space group P6{sub 2}22, with unit-cell parameters a = b = 136.0, c = 125.3 Å; they diffract to beyond 2.5 Å resolution using synchrotron radiation and contain one monomer in the asymmetric unit. The structure of CARM1{sub 28–507} was solved by multiple isomorphous replacement and anomalous scattering methods. Crystals of apo CARM1{sub 140–480} belong to space group I222, with unit-cell parameters a = 74.6, b = 99.0, c = 207.4 Å; they diffract to beyond 2.7 Å resolution and contain two monomers in the asymmetric unit. Crystals of CARM1{sub 140–480} in complex with S-adenosyl-l-homocysteine belong to space P2{sub 1}2{sub 1}2, with unit-cell parameters a = 74.6, b = 98.65, c = 206.08 Å; they diffract to beyond 2.6 Å resolution and contain four monomers in the asymmetric unit. The structures of apo and holo CARM1{sub 140–480} were solved by molecular-replacement techniques from the structure of CARM1{sub 28–507}.

Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

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María C Ortiz

Full Text Available The aim of this study was to evaluate whether L-Arginine (L-Arg supplementation modifies nitric oxide (NO system and consequently aquaporin-2 (AQP2 expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

The story of invasive algae, arginine, and turtle tumors does not make sense

Science.gov (United States)

Work, Thierry M.; Ackermann, Mathias; Casey, James W.; Chaloupka, Milani; Herbst, Lawrence; Lynch, Jennifer M.; Stacy, Brian A.

2014-01-01

We are presenting a rebuttal letter to the following article that appeared recently on PeerJ: Van Houtan KS, Smith CM, Dailer ML, and Kawachi M. 2014. Eutrophication and the dietary promotion of sea turtle tumors. PeerJ 2:e602. This article is available at the following URL: https://peerj.com/articles/602/. We argue that the article lacks an inferential framework to answer the complex question regarding the drivers of the turtle tumor disease fibropapillomatosis in Hawaii. The article also contains procedural flaws and does not provide any compelling evidence of a link between algae, arginine, and turtle tumors.

Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS

Science.gov (United States)

Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

2012-01-01

The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

Radioimmunoassay of arginine vasopressin in human plasma

International Nuclear Information System (INIS)

Uhlich, E.; Weber, P.; Groeschel-Stewart, U.; Roeschlau, T.; Wuerzburg Univ.

1975-01-01

Antibodies for the radioimmunoassay of arginine vasopressin (AVP) described here were produced in rabbits using synthetic AVP coupled to rabbit γ-globulin with carbodiimide. In three out of six rabbits, significant antibody titres were obtained. Using the best antisera produced, 40% of labelled AVP was bound at a final dilution of 1 : 50,000. After iodination of synthetic AVP with 125 I using the chloramin-T method, a gel filtration on Sephadex G-25 was performed to purify the iodinated AVP. For separation of antibody bound and free hormone, a second antibody precipitation was used. There was no crossreactivity with oxytocin. AVP was extracted from plasma after ammoniumsulfate precipitation of the proteins by adsorption to Florisil. The recovery of AVP added to plasma in amounts of 5-25 pg/ml was 60 +- 15% (n = 6). The minimum amount of AVP detectable was 1 pg per ml plasma. The plasma level in normal adults under standard conditions was 3.4 +- 2.2 pg/ml. This is in agreement with data recently published by other researchers. The applicability and reproducibility was further tested in measurements of samples taken hourly during the entire day under water diuresis and after hormonal stimulation of AVP. (orig.) [de

The L-alpha-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in L-arginine-induced insulin release

DEFF Research Database (Denmark)

Smajilovic, Sanela; Clemmensen, Christoffer; Johansen, Lars Dan

2013-01-01

insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism. In this study, we demonstrate that GPRC6A is expressed in islets of Langerhans, but activation of the receptor by L-arginine did not stimulate insulin secretion. We also investigated central...... metabolic parameters in GPRC6A knockout mice compared with wildtype littermates and found no difference in glucose metabolism or body fat percentage when mice were administered a standard chow diet. In conclusion, our data do not support a role for GPRC6A in L-arginine-induced insulin release and glucose...

Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases

Science.gov (United States)

Haupt, V. Joachim; Schroeder, Michael; Labudde, Dirk

2018-01-01

The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes. PMID:29659563

Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene.

Directory of Open Access Journals (Sweden)

Jungtae Na

Full Text Available Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5 as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene.

Crystallization and X-ray diffraction studies of arginine kinase from the white Pacific shrimp Litopenaeus vannamei

International Nuclear Information System (INIS)

Lopez-Zavala, Alonso A.; Sotelo-Mundo, Rogerio R.; Garcia-Orozco, Karina D.; Isac-Martinez, Felipe; Brieba, Luis G.; Rudiño-Piñera, Enrique

2012-01-01

The crystallization and preliminary X-ray diffraction analysis at 1.25 Å resolution of free-ligand arginine kinase from the Pacific whiteleg shrimp Litopenaeus vannamei are reported. Crystals belong to space group P2 1 2 1 2 1 , phases were determined by molecular replacement and refinement was performed with Phenix. Crystals of an unligated monomeric arginine kinase from the Pacific whiteleg shrimp Litopenaeus vannamei (LvAK) were successfully obtained using the microbatch method. Crystallization conditions and preliminary X-ray diffraction analysis to 1.25 Å resolution are reported. Data were collected at 100 K on NSLS beamline X6A. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 56.5, b = 70.2, c = 81.7 Å. One monomer per asymmetric unit was found, with a Matthews coefficient (V M ) of 2.05 Å 3 Da −1 and 40% solvent content. Initial phases were determined by molecular replacement using a homology model of LvAK as the search model. Refinement was performed with PHENIX, with final R work and R free values of 0.15 and 0.19, respectively. Biological analysis of the structure is currently in progress

Radio-immunoassay of plasma arginine vasopressin in man. Comparison of two methods of extraction

International Nuclear Information System (INIS)

Wolf, J.P.; Dumoulin, G.; Henriet, M.T.; Baulay, A.; Berthelay, S.

1987-01-01

Two methods of extraction, prior to radio-immunoassay (RIA) of human plasma arginine vasopressin (AVP) were tested: ethanol extraction (ETH), chromatography with ODS-Silice (ODS-Sil). Recovery of 125 I AVP was higher when using ODS-Sil than when using ETH. Recovery of standard AVP was found to be more efficient and reproducible for ODS-Sil. However, the RIA used, performed after chromatography with ODS-Sil, is not enough sensitive to detect low concentrations but is able to detect high concentrations and physiological variations of plasma AVP [fr

Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

Science.gov (United States)

Lotfipour, Shahrdad; Smith, Maree T

2018-01-01

Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

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Hüseyin Ilgü

2018-03-01

Full Text Available The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg, agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5, an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

[Effect of L-arginine and the nitric oxide synthase blocker L-NNA on calcium capacity in rat liver mitochondria with differing resistance to hypoxia].

Science.gov (United States)

Kurhaliuk, N M; Ikkert, O V; Vovkanych, L S; Horyn', O V; Hal'kiv, M O; Hordiĭ, S K

2001-01-01

The effect of L-arginine and blockator of nitric oxide synthase L-NNA on processes of calcium mitochondrial capacity in liver with different resistance to hypoxia in the experiments with Wistar rats has been studied using the followrng substrates of energy support: succinic, alpha-ketoglutaric acids, alpha-ketolutarate and inhibitor succinatedehydrogenase malonate. As well we used substrates mixtures combination providing for activation of aminotransferase mechanism: glutamate and piruvate, glutamate and malate. It has been shown that L-arginine injection increases calcium mitochondrial capacity of low resistant rats using as substrates the succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of donors nitric oxide on this processes limit NO-synthase inhibitor L-NNA.

Evaluation of novel arginine based inhibitors of DDAH and investigations into radical hydroacylation of vinyl sulfonates

OpenAIRE

Khanom, N.

2010-01-01

The thesis is in two main sections. In the first section, studies on methylarginine processing enzymes are presented. Dimethyalrginine dimethylaminohydrolase (DDAH) is a class of enzymes involved in the metabolism of methylarginines ADMA and L-NMMA, which indirectly regulate physiological nitric oxide levels. It is desirable to inhibit excess NO in pathological situations, and the arginine mimetic L-257 is a DDAH inhibitor which reduces levels of NO. Synthesis of ester analo...

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

Institute of Scientific and Technical Information of China (English)

Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi

2013-01-01

Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9％ NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain.

Science.gov (United States)

Moutaoufik, Mohamed Taha; Morrow, Geneviève; Maaroufi, Halim; Férard, Céline; Finet, Stéphanie; Tanguay, Robert M

2017-07-01

The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form. In vitro, the chaperone-like activity of wild-type DmHsp27 was comparable with that of its two isolated populations and to the single population of the R122G, R131G, and R135G using luciferase as substrate. However, using insulin, the chaperone-like activity of wild-type DmHsp27 was lower than that of R122G and R131G mutants. Altogether, the results characterize wild-type DmHsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of sHsps.

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

NARCIS (Netherlands)

Boertien, W. E.; Riphagen, I. J.; Drion, I.; Alkhalaf, A.; Bakker, S. J. L.; Groenier, K. H.; Struck, J.; de Jong, P. E.; Bilo, H. J. G.; Kleefstra, N.; Gansevoort, R. T.

Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. Plasma copeptin, a

Bioinformatic analysis of an unusual gene-enzyme relationship in the arginine biosynthetic pathway among marine gamma proteobacteria: implications concerning the formation of N-acetylated intermediates in prokaryotes

Directory of Open Access Journals (Sweden)

Labedan Bernard

2006-01-01

Full Text Available Abstract Background The N-acetylation of L-glutamate is regarded as a universal metabolic strategy to commit glutamate towards arginine biosynthesis. Until recently, this reaction was thought to be catalyzed by either of two enzymes: (i the classical N-acetylglutamate synthase (NAGS, gene argA first characterized in Escherichia coli and Pseudomonas aeruginosa several decades ago and also present in vertebrates, or (ii the bifunctional version of ornithine acetyltransferase (OAT, gene argJ present in Bacteria, Archaea and many Eukaryotes. This paper focuses on a new and surprising aspect of glutamate acetylation. We recently showed that in Moritella abyssi and M. profunda, two marine gamma proteobacteria, the gene for the last enzyme in arginine biosynthesis (argH is fused to a short sequence that corresponds to the C-terminal, N-acetyltransferase-encoding domain of NAGS and is able to complement an argA mutant of E. coli. Very recently, other authors identified in Mycobacterium tuberculosis an independent gene corresponding to this short C-terminal domain and coding for a new type of NAGS. We have investigated the two prokaryotic Domains for patterns of gene-enzyme relationships in the first committed step of arginine biosynthesis. Results The argH-A fusion, designated argH(A, and discovered in Moritella was found to be present in (and confined to marine gamma proteobacteria of the Alteromonas- and Vibrio-like group. Most of them have a classical NAGS with the exception of Idiomarina loihiensis and Pseudoalteromonas haloplanktis which nevertheless can grow in the absence of arginine and therefore appear to rely on the arg(A sequence for arginine biosynthesis. Screening prokaryotic genomes for virtual argH-X 'fusions' where X stands for a homologue of arg(A, we retrieved a large number of Bacteria and several Archaea, all of them devoid of a classical NAGS. In the case of Thermus thermophilus and Deinococcus radiodurans, the arg(A-like sequence

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

Science.gov (United States)

Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

2017-05-17

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

Analogues of arginine vasopressin (AVP) modified inthe N-terminal part of the molecule with stereoisomers of 4-aminopyroglutamic acid

Czech Academy of Sciences Publication Activity Database

Sobolewski, D.; Kowalczyk, W.; Derdowska, I.; Slaninová, Jiřina; Zabrocki, J.; Lammek, B.

2005-01-01

Roč. 79, č. 4 (2005), 731-737 ISSN 0137- 5083 Grant - others:PSCSR(PL) KBN6P05F01021; PSCSR(PL) BW8000-5-0222-3 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin (AVP) * oxytocin * 4-aminopyroglutamic acid Subject RIV: CE - Biochemistry Impact factor: 0.513, year: 2005

Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

Science.gov (United States)

Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

2013-09-01

Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery.

Science.gov (United States)

Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton

2017-11-01

The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase equilibria in a system of aqueous arginine with an octane solution of sulfonic acid

Science.gov (United States)

Kuvaeva, Z. I.; Koval'chuk, I. V.; Vodop'yanova, L. A.; Soldatov, V. S.

2013-05-01

The extraction of arginine (Arg) from aqueous salt (0.1 M NaCl) solutions with a sulfo extractant in a wide range of pH values and amino acid concentrations was studied. The 0.1 M solution of dinonylnaphthalenesulfonic acid (HD) in octane was used as an extractant. The degree of extraction was found to be high at pH 0.8-9.0. This can be explained by the effect of additional intermolecular interactions in the extractant phase involving the guanidine group of Arg.

Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

International Nuclear Information System (INIS)

Wang, Biao; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Liu, Yang

2015-01-01

Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

Energy Technology Data Exchange (ETDEWEB)

Wang, Biao [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Feng, Lin; Jiang, Wei-Dan [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Wu, Pei [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Kuang, Sheng-Yao [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Jiang, Jun [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Tang, Ling; Tang, Wu-Neng [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Zhang, Yong-An [Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Liu, Yang, E-mail: kyckgk@hotmail.com [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); and others

2015-01-15

Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different Gram-positive bacteria

NARCIS (Netherlands)

Meissner, Daniel; Vollstedt, Angela; van Dijl, Jan Maarten; Freudl, Roland

In contrast to the general protein secretion (Sec) system, the twin-arginine translocation (Tat) export pathway allows the translocation of proteins across the bacterial plasma membrane in a fully folded conformation. Due to this feature, the Tat pathway provides an attractive alternative to the

Arginine vasopressin and its analogues--the influence of position 2 modification with 3,3-diphenylalanine enantiomers. Highly potent V2 agonists

Czech Academy of Sciences Publication Activity Database

Kwiatkowska, A.; Sobolewski, D.; Prahl, A.; Borovičková, Lenka; Slaninová, Jiřina; Lammek, B.

2009-01-01

Roč. 44, č. 7 (2009), s. 2862-2867 ISSN 0223-5234 Institutional research plan: CEZ:AV0Z40550506 Keywords : arginine vasopressin analogues * AVP * 3,3-diphenylalanine enantiomers * V2 agonists * antidiuretic activity Subject RIV: CC - Organic Chemistry Impact factor: 3.269, year: 2009

Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

Science.gov (United States)

Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

2018-03-20

The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

Systemic inflammation is linked to low arginine and high ADMA plasma levels resulting in an unfavourable NOS substrate-to-inhibitor ratio: the Hoorn Study

NARCIS (Netherlands)

van der Zwan, L.P.; Scheffer, P.G.; Dekker, J.M.; Stehouwer, C.D.A.; Heine, R.J.; Teerlink, T.

2011-01-01

Inflammation is associated with a reduced availability of NO in the vasculature. We investigated the possible involvement of altered levels of the substrate (arginine) and the inhibitor [ADMA (asymmetric ω-N

Mutations in the codon for a conserved arginine-1563 in the COL4A5 collagen gene in Alport syndrome

DEFF Research Database (Denmark)

Zhou, J; Gregory, M C; Hertz, Jens Michael

1993-01-01

for arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members....

Life on arginine for Mycoplasma hominis: clues from its minimal genome and comparison with other human urogenital mycoplasmas.

Directory of Open Access Journals (Sweden)

Sabine Pereyre

2009-10-01

Full Text Available Mycoplasma hominis is an opportunistic human mycoplasma. Two other pathogenic human species, M. genitalium and Ureaplasma parvum, reside within the same natural niche as M. hominis: the urogenital tract. These three species have overlapping, but distinct, pathogenic roles. They have minimal genomes and, thus, reduced metabolic capabilities characterized by distinct energy-generating pathways. Analysis of the M. hominis PG21 genome sequence revealed that it is the second smallest genome among self-replicating free living organisms (665,445 bp, 537 coding sequences (CDSs. Five clusters of genes were predicted to have undergone horizontal gene transfer (HGT between M. hominis and the phylogenetically distant U. parvum species. We reconstructed M. hominis metabolic pathways from the predicted genes, with particular emphasis on energy-generating pathways. The Embden-Meyerhoff-Parnas pathway was incomplete, with a single enzyme absent. We identified the three proteins constituting the arginine dihydrolase pathway. This pathway was found essential to promote growth in vivo. The predicted presence of dimethylarginine dimethylaminohydrolase suggested that arginine catabolism is more complex than initially described. This enzyme may have been acquired by HGT from non-mollicute bacteria. Comparison of the three minimal mollicute genomes showed that 247 CDSs were common to all three genomes, whereas 220 CDSs were specific to M. hominis, 172 CDSs were specific to M. genitalium, and 280 CDSs were specific to U. parvum. Within these species-specific genes, two major sets of genes could be identified: one including genes involved in various energy-generating pathways, depending on the energy source used (glucose, urea, or arginine and another involved in cytadherence and virulence. Therefore, a minimal mycoplasma cell, not including cytadherence and virulence-related genes, could be envisaged containing a core genome (247 genes, plus a set of genes required for

The protective effect of NG-nitro-L-arginine methyl ester and insulin on nitric oxide inhibition and pathology in experimental diabetic rat liver

International Nuclear Information System (INIS)

Ozden, H.; Guven, G.; Tekin, N.; Akyuz, F.; Gurer, F.; Kucuk, F.; Ustuner, Mehmet C.; Yaylak, F.

2009-01-01

Objective was to determine on protective role of NG-nitro-L-arginine methyl ester (L-NAME) and insulin on the liver in streptoozotocin (STZ) induced diabetic rats. This study was performed in the Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. Forty male Wistar albino rats were divided into 5 groups. These were untreated, diabetic control, STZ+insulin, STZ+L-NAME and STZ+insulin+L-NAME induced groups. The STZ was intraperitonally injected into 3 groups and includes insulin, L-NAME and their joint administrations as protective agents. The blood glucose and nitric oxide (NO) levels were determined. The tissue samples were obtained at the end of the fourth week. The liver tissue distortions were evaluated using hematoxylin and eosin staining. The serum glucose level was significantly higher in diabetic control (p=0.000), than the untreated group. The focal pseudo lobular structures without vena centralis increased portal fibrillary necrosis and bile duct stenosis with voagulation necrosis of the peripheral hepatocytes were more observed in diabetic group than the protective agent groups. In addition, insulin and L-NAME lead to hepatocyte regeneration and minimal mononuclear cell infiltration was noted. NG-nitro-L-arginine methyl ester inhibits NO level in STZ+L-NAME induced group. NG-nitro-L-arginine methyl ester either alone or with insulin combination significantly attenuates the liver morphological disarrangements in STZ induced diabetic rats. (author)

Comparison of the effects of NG-nitro-L-arginine and indomethacin on the hypercapnic cerebral blood flow increase in rats

DEFF Research Database (Denmark)

Wang, Qian; Pelligrino, D A; Paulson, O B

1994-01-01

The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF...... with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg....../kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7...

Structures of the N47A and E109Q mutant proteins of pyruvoyl-dependent arginine decarboxylase from Methanococcus jannaschii

International Nuclear Information System (INIS)

Soriano, Erika V.; McCloskey, Diane E.; Kinsland, Cynthia; Pegg, Anthony E.; Ealick, Steven E.

2008-01-01

The crystal structures of two arginine decarboxylase mutant proteins provide insights into the mechanisms of pyruvoyl-group formation and the decarboxylation reaction. Pyruvoyl-dependent arginine decarboxylase (PvlArgDC) catalyzes the first step of the polyamine-biosynthetic pathway in plants and some archaebacteria. The pyruvoyl group of PvlArgDC is generated by an internal autoserinolysis reaction at an absolutely conserved serine residue in the proenzyme, resulting in two polypeptide chains. Based on the native structure of PvlArgDC from Methanococcus jannaschii, the conserved residues Asn47 and Glu109 were proposed to be involved in the decarboxylation and autoprocessing reactions. N47A and E109Q mutant proteins were prepared and the three-dimensional structure of each protein was determined at 2.0 Å resolution. The N47A and E109Q mutant proteins showed reduced decarboxylation activity compared with the wild-type PvlArgDC. These residues may also be important for the autoprocessing reaction, which utilizes a mechanism similar to that of the decarboxylation reaction

Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study.

Science.gov (United States)

Wu, De-Qun; Zhu, Jie; Han, Hua; Zhang, Jun-Zhi; Wu, Fei-Fei; Qin, Xiao-Hong; Yu, Jian-Yong

2018-01-01

A multi-functional hybrid hydrogel P(M-Arg/NIPAAm) with temperature response, anti-protein adsorption and antibacterial properties was prepared and applied as wound dressing. The hydrogel was carried out by free radical copolymerization of methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm) monomers using N,N'-methylene bisacrylamide as a crosslinker, and ammonium persulfate/N,N,N', N'-tetramethylethylenediamine as the redox initiator. To endow the antimicrobial property, chlorhexidine diacetate (CHX) was preloaded into the hydrogel and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively. The antimicrobial property of two series of hydrogels was evaluated and compared. The successful synthesis of M-Arg, PHMG and hydrogels was proved by 13 C NMR, 1 H NMR and FTIR spectroscopy. The hydrogel morphology characterized by scanning electron microscopy confirmed that the homogeneous porous and interconnected structures of the hydrogels. The swelling, protein adsorption property, in vitro release of CHX, antimicrobial assessment, cell viability as well as in vivo wound healing in a mouse model were studied. The results showed the nontoxicity and antimicrobial P(M-Arg/NIPAAm) hydrogel accelerated the full-thickness wound healing process and had the potential application in wound dressing. Despite the zwitterionic characteristic and biocompatible property of arginine based hydrogels, the brittle behavior and non-transparency still remain as a significant problem for wound dressing. Furthermore promoting the antibacterial property of the zwitterionic hydrogel is also necessary to prevent the bacterial colonization and subsequent wound infection. Therefore, we created a hybrid hydrogel combined methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm). NIPAAm improves transparency and mechanical property as well as acts as a temperature-response drug release system. Additionally, chlorhexidine (CHX) was preloaded

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

Directory of Open Access Journals (Sweden)

Sonia Alves Gouvea

2014-01-01

Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

Science.gov (United States)

Yang, Jun; Chen, Jian-Min; Liu, Wen-Yan; Song, Cao-You; Wang, Cheng-Hai; Lin, Bao-Cheng

2006-09-01

Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

Dietary supplementation with arginine and glutamic acid enhances key lipogenic gene expression in growing pigs.

Science.gov (United States)

Hu, C J; Jiang, Q Y; Zhang, T; Yin, Y L; Li, F N; Su, J Y; Wu, G Y; Kong, X F

2017-12-01

Our previous study showed dietary supplementation with Arg and Glu increased intramuscular fat deposition and decreased back fat thickness in pigs, suggesting that the genes involved in lipid metabolism might be regulated differently in muscle and s.c. adipose (SA) tissues. Sixty Duroc × Large White × Landrace pigs with an average initial BW of 77.1 ± 1.3 kg were randomly assigned to 1 of 5 treatment groups (castrated male to female ratio = 1:1). Pigs in the control group were fed a basic diet, and those in experimental groups were fed the basic diet supplemented with 2.05% alanine (isonitrogenous group), 1.00% arginine (Arg group), 1.00% glutamic acid + 1.44% alanine (Glu group), or 1.00% arginine + 1.00% glutamic acid (Arg+Glu group). Fatty acid percentages and mRNA expression levels of the genes involved in lipid metabolism in muscle and SA tissues were examined. The percentages of C14:0 and C16:0 in the SA tissue of Glu group pigs and C14:0 in the longissimus dorsi (LD) muscle of Glu and Arg+Glu groups decreased ( acid synthase in the Arg+Glu group was more upregulated ( < 0.05) than that of the Arg group. An increase in the mRNA level of in the biceps femoris muscle was also observed in the Arg+Glu group ( < 0.05) compared with the basic diet and isonitrogenous groups. Collectively, these findings suggest that dietary supplementation with Arg and Glu upregulates the expression of genes involved in adipogenesis in muscle tissues and lipolysis in SA tissues.

Arginine kinase in Toxocara canis: Exon-intron organization, functional analysis of site-directed mutants and evaluation of putative enzyme inhibitors.

Science.gov (United States)

Wickramasinghe, Susiji; Yatawara, Lalani; Nagataki, Mitsuru; Agatsuma, Takeshi

2016-10-01

To determine exon/intron organization of the Toxocara canis (T. canis) AK (TCAK) and to test green and black tea and several other chemicals against the activity of recombinant TCAK in the guanidino-specific region by site-directed mutants. Amplification of genomic DNA fragments containing introns was carried out by PCRs. The open-reading frame (1200 bp) of TCAK (wild type) was cloned into the BamH1/SalI site of pMAL-c2X. The maltose-binding protein-TCAK fusion protein was expressed in Escherichia coli TB1 cells. The purity of the expressed enzyme was verified by SDS-PAGE. Mutations were introduced into the guanidino-specific region and other areas of pMAL/TCAK by PCR. Enzyme activity was measured with an NADH-linked assay at 25 °C for the forward reaction (phosphagen synthesis). Arginine kinase in T. canis has a seven-exon/six-intron gene structure. The lengths of the introns ranged from 542 bp to 2 500 bp. All introns begin with gt and end with ag. Furthermore, we measured the enzyme activity of site-directed mutants of the recombinant TCAK. The K m value of the mutant (Alanine to Serine) decreased indicating a higher affinity for substrate arginine than the wild-type. The K m value of the mutant (Serine to Glycine) increased to 0.19 mM. The K m value (0.19 mM) of the double mutant (Alanine-Serine to Serine-Glycine) was slightly greater than in the wild-type (0.12 mM). In addition, several other chemicals were tested; including plant extract Azadiracta indica (A. indica), an aminoglycoside antibiotic (aminosidine), a citrus flavonoid glycoside (rutin) and a commercially available catechin mixture against TCAK. Green and black tea (1:10 dilution) produced 15% and 25% inhibition of TCAK, respectively. The extract of A. indica produced 5% inhibition of TCAK. Moreover, green and black tea produced a non-competitive type of inhibition and A. indica produced a mixed-type of inhibition on TCAK. Arginine kinase in T. canis has a seven-exon/six-intron gene

Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular and all-cause mortality in patients with type 2 diabetes (ZODIAC-31)

NARCIS (Netherlands)

Riphagen, Ineke J.; Boertien, Wendy E.; Alkhalaf, Alaa; Kleefstra, Nanno; Gansevoort, Ron T.; Groenier, Klaas H.; van Hateren, Kornelis J. J.; Struck, Joachim; Navis, Gerjan; Bilo, Henk J. G.; Bakker, Stephan J. L.

2013-01-01

OBJECTIVE: Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim

The bidirectional phase-shifting effects of melatonin on the arginine vasopressin secretion rhythm in rat suprachiasmatic nuclei in vitro

Czech Academy of Sciences Publication Activity Database

Svobodová, Irena; Vaněček, Jiří; Zemková, Hana

2003-01-01

Roč. 116, 1-2 (2003), s. 80-85 ISSN 0169-328X R&D Projects: GA ČR GA309/02/1519; GA ČR GA309/02/1479; GA AV ČR IAA5011103; GA AV ČR IAA5011105 Institutional research plan: CEZ:AV0Z5011922 Keywords : melatonin * arginine vasopressin * circadian rhythm Subject RIV: ED - Physiology Impact factor: 2.107, year: 2003

Control of utilization of L-arginine, L-ornithine, agmatine, and putrescine as nitrogen sources in Escherichia coli K-12.

OpenAIRE

Shaibe, E; Metzer, E; Halpern, Y S

1985-01-01

The regulation of the synthesis of the enzymes involved in the utilization of L-arginine, L-ornithine, agmatine, and putrescine as a sole nitrogen source in Escherichia coli K-12 was examined. The synthesis of agmatine ureohydrolase, putrescine aminotransferase, and pyrroline dehydrogenase is dually controlled by catabolite repression and nitrogen availability. Catabolite repression of agmatine ureohydrolase, but not that of putrescine aminotransferase or pyrroline dehydrogenase, is relieved ...

Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders

Directory of Open Access Journals (Sweden)

Derek W. Stouth

2017-11-01

Full Text Available Protein arginine methyltransferases (PRMTs are a family of enzymes that catalyze the methylation of arginine residues on target proteins, thereby mediating a diverse set of intracellular functions that are indispensable for survival. Indeed, full-body knockouts of specific PRMTs are lethal and PRMT dysregulation has been implicated in the most prevalent chronic disorders, such as cancers and cardiovascular disease (CVD. PRMTs are now emerging as important mediators of skeletal muscle phenotype and plasticity. Since their first description in muscle in 2002, a number of studies employing wide varieties of experimental models support the hypothesis that PRMTs regulate multiple aspects of skeletal muscle biology, including development and regeneration, glucose metabolism, as well as oxidative metabolism. Furthermore, investigations in non-muscle cell types strongly suggest that proteins, such as peroxisome proliferator-activated receptor-γ coactivator-1α, E2F transcription factor 1, receptor interacting protein 140, and the tumor suppressor protein p53, are putative downstream targets of PRMTs that regulate muscle phenotype determination and remodeling. Recent studies demonstrating that PRMT function is dysregulated in Duchenne muscular dystrophy (DMD, spinal muscular atrophy (SMA, and amyotrophic lateral sclerosis (ALS suggests that altering PRMT expression and/or activity may have therapeutic value for neuromuscular disorders (NMDs. This review summarizes our understanding of PRMT biology in skeletal muscle, and identifies uncharted areas that warrant further investigation in this rapidly expanding field of research.

Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men.

Science.gov (United States)

Wax, Benjamin; Kavazis, Andreas N; Webb, Heather E; Brown, Stanley P

2012-04-17

Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG) muscular strength and endurance in resistance trained and untrained men. Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM) on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Our data showed statistical significant differences (p0.05) between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

L-Arginine modified multi-walled carbon nanotube/sulfonated poly(ether ether ketone) nanocomposite films for biomedical applications

Science.gov (United States)

Kaya, Hatice; Bulut, Osman; Kamali, Ali Reza; Ege, Duygu

2018-06-01

Favorable implant-tissue interactions are crucial to achieve successful osseointegration of the implants. Poly(ether ether ketone) (PEEK) is an interesting alternative to titanium in orthopedics because of its low cost, high biocompatibility and comparable mechanical properties with cancellous bone. Despite these advantages; however, the untreated surface of PEEK fails to osseointegrate due to its bioinert and hydrophobic behavior. This paper deals with the surface modification of PEEK with a novel method. For this, PEEK was first treated with concentrated sulfuric acid to prepare sulfonated PEEK (SPEEK) films using a solvent casting method. Then, 1 and 2 wt% multi-walled carbon nanotube was incorporated into SPEEK to form nanocomposite films. The samples were characterized with Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy. After successful preparation of the nanocomposite films, L-arginine was covalently conjugated on the nanocomposite films to further improve their surface properties. Subsequently, the samples were characterized using X-ray Photoemission Spectroscopy (XPS), water contact angle measurements and Atomic Force Microscopy (AFM) and Dynamic Mechanical Thermal Analysis (DMTA). Finally, cell culture studies were carried out by using Alamar Blue assay to evaluate the biocompatibility of the films. The results obtained indicate the successful preparation of L-arginine-conjugated MWCNT/SPEEK nanocomposite films. The modified surface shows potential to improve implants' mechanical and biological performances.

Participation of the arcRACME protein in self-activation of the arc operon located in the arginine catabolism mobile element in pandemic clone USA300.

Science.gov (United States)

Rozo, Zayda Lorena Corredor; Márquez-Ortiz, Ricaurte Alejandro; Castro, Betsy Esperanza; Gómez, Natasha Vanegas; Escobar-Pérez, Javier

2017-07-01

Staphylococcus aureus pandemic clone USA300 has, in addition to its constitutive arginine catabolism (arc) gene cluster, an arginine catabolism mobile element (ACME) carrying another such cluster, which gives this clone advantages in colonisation and infection. Gene arcR, which encodes an oxygen-sensitive transcriptional regulator, is inside ACME and downstream of the constitutive arc gene cluster, and this situation may have an impact on its activation. Different relative expression behaviours are proven here for arcRACME and the arcACME operon compared to the constitutive ones. We also show that the artificially expressed recombinant ArcRACME protein binds to the promoter region of the arcACME operon; this mechanism can be related to a positive feedback model, which may be responsible for increased anaerobic survival of the USA300 clone during infection-related processes.

Deceleration of arginine kinase refolding by induced helical structures.

Science.gov (United States)

Li, Hai-Long; Zhou, Sheng-Mei; Park, Daeui; Jeong, Hyoung Oh; Chung, Hae Young; Yang, Jun-Mo; Meng, Fan-Guo; Hu, Wei-Jiang

2012-04-01

Arginine kinase (AK) is a key metabolic enzyme for keeping energy balance in invertebrates. Therefore, regulation of the enzymatic activity and the folding studies of AK from the various invertebrates have been the focus of investigation. We studied the effects of helical structures by using hexafluoroisopropanol (HFIP) on AK folding. Folding kinetic studies showed that the folding rates of the urea-denatured AKs were significantly decelerated after being induced in various concentrations of HFIP. AK lost its activity completely at concentrations greater than 60%. The results indicated that the HFIP-induced helical structures in the denatured state play a negative role in protein folding, and the helical structures induced in 5% (v/v) HFIP act as the most effective barrier against AK taking its native structure. The computational docking simulations (binding energies for -2.19 kcal/mol for AutoDock4.2 and -20.47 kcal/mol for Dock6.3) suggested that HFIP interacts with the several important residues that are predicted by both programs. The excessively pre-organized helical structures not only hampered the folding process, but also ultimately brought about changes in the three-dimensional conformation and biological function of AK.

Content of non-esterified fatty acids in the blood plasma of rabbits with acute arginine pancreatitis and its correction

Directory of Open Access Journals (Sweden)

Y. F. Rivis

2013-01-01

Full Text Available The aim of this work was to study the content of non-esterified fatty acids in plasma and liver of rabbits with acute arginine pancreatitis and its correction by linseed oil. The experiment was carried out on male rabbits breed gray giant with live weight 3.8–4.0 kg. The material for the study was sampled from blood and liver. Lipids from plasma and liver were extracted with a mixture of chloroform and methanol. After that the non-esterified fatty acids were isolated and methylated. Methyl esters of fatty acids were studied by the gas-liquid chromatography with the chromatograph ''Chrom 5'' (Prague,CzechRepublic. We have found that the content of non-esterified fatty acids decreases in the blood plasma and liver of rabbits with the acute arginine pancreatitis. It takes place at the expense of a reduce of saturated fatty acids with odd and even number of carbon atoms in a chain, monounsaturated fatty acids of the families ω-7 and ω-9 and polyunsaturated fatty acids of the families ω-3 and ω-6. That may indicate a greater use of non-esterified fatty acids for energy metabolism and esterification of lipids. We suppose that this is a consequence of the probable increase in content of non-esterified and esterified cholesterol in the rabbits’ blood plasma. Those processes provoke the cholesterol deposits in blood vessels and therefore cardiovascular diseases. We tried to influence on the processes by addition of linseed oil to the rabbits diet. We have found that in the linseed oil-fed rabbits the content of non-esterified fatty acids decreases at the expense of saturated fatty acids with odd and even number of carbon atoms in a chain and monounsaturated fatty acids of the families ω-7 and ω-9 inblood plasma and liver of the rabbits with acute arginine pancreatitis. Furthermore the levels of non-esterified polyunsaturated fatty acids of ω-3 family increase in the rabbits’ plasma and liver. As this takes place the ratio of non

New role for L-arginine in regulation of inducible nitric-oxide-synthase-derived superoxide anion production in Raw 264.7 macrophages

Czech Academy of Sciences Publication Activity Database

Pekarová, Michaela; Lojek, Antonín; Martíšková, Hana; Vašíček, Ondřej; Binó, Lucia; Klinke, A.; Lau, D.; Kuchta, R.; Kadlec, J.; Vrba, R.; Kubala, Lukáš

2011-01-01

Roč. 11, - (2011), s. 2443-2457 ISSN 1537-744X R&D Projects: GA ČR(CZ) GA524/08/1753 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : macrophage s * L-arginine * inducible nitric oxide synthase Subject RIV: BO - Biophysics Impact factor: 1.524, year: 2010

The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D2 Dopamine Receptor (D2L-R Acts as an Intracellular Retention Signal

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Valentina Kubale

2016-07-01

Full Text Available This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D2 dopamine receptor (D2L-R confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR located within the insert could act as an RXR-type endoplasmic reticulum (ER retention signal. Arginine residues (R within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E, either individually or in clusters, thus generating single, double, and triple D2L-R mutants. Through analyses of cellular localization by confocal microscopy and enzyme-linked immunosorbent assay (ELISA, radioligand binding assay, bioluminescence resonance energy transfer (BRET2 β-arrestin 2 (βarr2 recruitment assay, and cAMP signaling, it was revealed that charge reversal of the R residues at all three positions within the motif impaired their colocalization with ER marker calnexin and led to significantly improved cell surface expression. Additionally, these data demonstrate that an R to glutamic acid (E substitution at position 2 within the RXR motif is not functionally permissible. Furthermore, all generated D2L-R mutants preserved their functional integrity regarding ligand binding, agonist-induced βarr2 recruitment and Gαi-mediated signaling. In summary, our results show that the conserved arginine cluster within the 29-amino acid insert of third cytoplasmic loop (IC3 of the D2L-R appears to be the ER retention signal.

Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation

International Nuclear Information System (INIS)

Sheng, Xiumei; Wang, Zhengxin

2016-01-01

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation. The online version of this article (doi:10.1186/s12885-016-2632-3) contains supplementary material, which is available to authorized users

Mutation of exposed hydrophobic amino acids to arginine to increase protein stability

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Czaplicki Jerzy

2004-07-01

Full Text Available Abstract Background One strategy to increase the stability of proteins is to reduce the area of water-accessible hydrophobic surface. Results In order to test it, we replaced 14 solvent-exposed hydrophobic residues of acetylcholinesterase by arginine. The stabilities of the resulting proteins were tested using denaturation by high temperature, organic solvents, urea and by proteolytic digestion. Conclusion Altough the mutational effects were rather small, this strategy proved to be successful since half of the mutants showed an increased stability. This stability may originate from the suppression of unfavorable interactions of nonpolar residues with water or from addition of new hydrogen bonds with the solvent. Other mechanisms may also contribute to the increased stability observed with some mutants. For example, introduction of a charge at the surface of the protein may provide a new coulombic interaction on the protein surface.

Interfacial electrostatics of poly(vinylamine hydrochloride), poly(diallyldimethylammonium chloride), poly-l-lysine, and poly-l-arginine interacting with lipid bilayers.

Science.gov (United States)

McGeachy, A C; Dalchand, N; Caudill, E R; Li, T; Doğangün, M; Olenick, L L; Chang, H; Pedersen, J A; Geiger, F M

2018-04-25

Charge densities of cationic polymers adsorbed to lipid bilayers are estimated from second harmonic generation (SHG) spectroscopy and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. The systems surveyed included poly(vinylamine hydrochloride) (PVAm), poly(diallyldimethylammonium chloride) (PDADMAC), poly-l-lysine (PLL), and poly-l-arginine (PLR), as well as polyalcohol controls. Upon accounting for the number of positive charges associated with each polyelectrolyte, the binding constants and apparent free energies of adsorption as estimated from SHG data are comparable despite differences in molecular masses and molecular structure, with ΔGads values of -61 ± 2, -58 ± 2, -57 ± 1, -52 ± 2, -52 ± 1 kJ mol-1 for PDADMAC400, PDADMAC100, PVAm, PLL, and PLR, respectively. Moreover, we find charge densities for polymer adlayers of approximately 0.3 C m-2 for poly(diallyldimethylammonium chloride) while those of poly(vinylamine) hydrochloride, poly-l-lysine, and poly-l-arginine are approximately 0.2 C m-2. Time-dependent studies indicate that polycation adsorption to supported lipid bilayers is only partially reversible for most of the polymers explored. Poly(diallyldimethylammonium chloride) does not demonstrate reversible binding even over long timescales (>8 hours).

Radioimmunoassay of arginine-vasopressin in human urine and its use in physiological and pathological states

International Nuclear Information System (INIS)

Khokhar, A.M.; Ramaga, C.M.; Slater, J.D.H.

1978-01-01

A highly specific radioimmunoassay for arginine-vasopressin (AVP) in human urine has been developed with a detection limit of 2.2 fmol/ml. The mean recovery of added AVP was 99.5 +- 3.1 (S.D.) % when correction was made for the fact that an inverse relationship was observed between the recovery of AVP and the osmolarity of the urine. The intra- and interassay coefficients of variation were 3.5 - 7 and 2.5 - 10% respectively. Arginine-vasopressin remains stable in urine after repeated freezing and thawing after storage at 4 or 20 0 C for up to 7 days and at 20 0 C for more than 3 months. During unrestricted fluid intake in normal people, the mean rate of renal excretion of AVP was 95 +- 68 (SD) fmol/min. An osmotic reduction of 9% in the plasma volume increased the excretion of AVP to 259 +- 147 (SD) fmol/min. Fluid deprivation for 18 h produced a moderate but significant increase in mean excretion of AVP, to a value of 116 +- 67 (SD) fmol/min. Patients with compulsive water drinking showed a normal relationship between urine osmolarity and the rate of excretion of AVP. In pituitary diabetes insipidus, AVP was undetectable, whereas in hereditary nephrogenic diabetes insipidus a progressive increase in the rate of excretion was observed in response to dehydration. There was a wide variation in the rate of excretion of AVP (range 126 - 8704 fmol/min) in patients with unexplained hyponatraemia, presumed to be due to an inappropriate secretion of antidiuretic hormone. Despite this variation, the relationship between urine osmolarity and the rate of excretion of AVP differed from that observed in normal people. (author)

Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats

Science.gov (United States)

Nagahama, Kenji; Nishio, Hikaru; Yamato, Masanori; Takeuchi, Koji

2012-01-01

Summary Background Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats. Material/Methods After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor. Results The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action. Conclusions The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide. PMID:22207112

Role of Arginine decarboxylase (ADC) in Arabidopsis thaliana defence against the pathogenic bacterium Pseudomonas viridiflava.

Science.gov (United States)

Rossi, F R; Marina, M; Pieckenstain, F L

2015-07-01

Polyamine biosynthesis starts with putrescine production through the decarboxylation of arginine or ornithine. In Arabidopsis thaliana, putrescine is synthesised exclusively by arginine decarboxylase (ADC), which exists as two isoforms (ADC1 and 2) that are differentially regulated by abiotic stimuli, but their role in defence against pathogens has not been studied in depth. This work analysed the participation of ADC in Arabidopsis defence against Pseudomonas viridiflava. ADC activity and expression, polyamine levels and bacterial resistance were analysed in null mutants of each ADC isoform. In non-infected wild-type (WT) plants, ADC2 expression was much higher than ADC1. Analysis of adc mutants demonstrated that ADC2 contributes to a much higher extent than ADC1 to basal ADC activity and putrescine biosynthesis. In addition, adc2 mutants showed increased basal expression of salicylic acid- and jasmonic acid-dependent PR genes. Bacterial infection induced putrescine accumulation and ADC1 expression in WT plants, but pathogen-induced putrescine accumulation was blocked in adc1 mutants. Results suggest a specific participation of ADC1 in defence, although basal resistance was not decreased by dysfunction of either of the two ADC genes. In addition, and as opposed to WT plants, bacterial infection increased ADC2 expression and ADC activity in adc1 mutants, which could counterbalance the lack of ADC1. Results demonstrate a major contribution of ADC2 to total ADC activity and the specific induction of ADC1 in response to infection. A certain degree of functional redundancy between the two isoforms in relation to their contribution to basal resistance is also evident. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Branched-Chain Amino Acids and Arginine Improve Performance in Two Consecutive Days of Simulated Handball Games in Male and Female Athletes: A Randomized Trial

Science.gov (United States)

Chang, Chen-Kang; Chang Chien, Kun-Ming; Chang, Jung-Hsien; Huang, Mei-Hsuan; Liang, Ya-Chuan; Liu, Tsung-Han

2015-01-01

The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA) and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days. Methods: Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial), or placebo (PB trial) before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34±0.60%, PB trial: -0.21±0.69%; second half: AA trial: -1.68±0.58%, PB trial: 0.49±0.42%). The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2±0.3) than the PB trial (15.1±0.4). Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue. PMID:25803783

Branched-chain amino acids and arginine improve performance in two consecutive days of simulated handball games in male and female athletes: a randomized trial.

Directory of Open Access Journals (Sweden)

Chen-Kang Chang

Full Text Available The central nervous system plays a crucial role in the development of physical fatigue. The purpose of this study is to investigate the effect of combined supplementation of branched-chain amino acids (BCAA and arginine on intermittent sprint performance in simulated handball games on 2 consecutive days.Fifteen male and seven female handball players consumed 0.17 g/kg BCAA and 0.04 g/kg arginine together (AA trial, or placebo (PB trial before exercise. Each trial contained two 60-min simulated handball games on consecutive days. The game was consisted of 30 identical 2-min blocks and a 20 m all-out sprint was performed at the end of each block. The performance, measured by percentage changes of sprint time between day 1 and 2, was significantly better in the AA trial (first half: AA trial: -1.34 ± 0.60%, PB trial: -0.21 ± 0.69%; second half: AA trial: -1.68 ± 0.58%, PB trial: 0.49 ± 0.42%. The average ratings of perceive exertion throughout the 2-day trial was significantly lower in the AA trial (14.2 ± 0.3 than the PB trial (15.1 ± 0.4. Concurrently, post-exercise tryptophan/BCAA ratio on both days in the AA trial was significantly lower than the baseline. This study showed that BCAA and arginine supplementation could improve performance in intermittent sprints on the second consecutive day of simulated handball games in well-trained athletes by potentially alleviating central fatigue.

Functionality of promoter microsatellites of arginine vasopressin receptor 1A (AVPR1A): implications for autism

LENUS (Irish Health Repository)

Tansey, Katherine E

2011-03-31

Abstract Background Arginine vasopressin (AVP) has been hypothesized to play a role in aetiology of autism based on a demonstrated involvement in the regulation of social behaviours. The arginine vasopressin receptor 1A gene (AVPR1A) is widely expressed in the brain and is considered to be a key receptor for regulation of social behaviour. Moreover, genetic variation at AVPR1A has been reported to be associated with autism. Evidence from non-human mammals implicates variation in the 5\\'-flanking region of AVPR1A in variable gene expression and social behaviour. Methods We examined four tagging single nucleotide polymorphisms (SNPs) (rs3803107, rs1042615, rs3741865, rs11174815) and three microsatellites (RS3, RS1 and AVR) at the AVPR1A gene for association in an autism cohort from Ireland. Two 5\\'-flanking region polymorphisms in the human AVPR1A, RS3 and RS1, were also tested for their effect on relative promoter activity. Results The short alleles of RS1 and the SNP rs11174815 show weak association with autism in the Irish population (P = 0.036 and P = 0.008, respectively). Both RS1 and RS3 showed differences in relative promoter activity by length. Shorter repeat alleles of RS1 and RS3 decreased relative promoter activity in the human neuroblastoma cell line SH-SY5Y. Conclusions These aligning results can be interpreted as a functional route for this association, namely that shorter alleles of RS1 lead to decreased AVPR1A transcription, which may proffer increased susceptibility to the autism phenotype.

Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men

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Wax Benjamin

2012-04-01

Full Text Available Abstract Background Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG muscular strength and endurance in resistance trained and untrained men. Methods Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Results Our data showed statistical significant differences (p0.05 between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. Conclusion The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa

Science.gov (United States)

McCurtain, Jennifer L.; Gilbertsen, Adam J.; Kalstabakken, Kyle A.; Williams, Bryan J.

2018-01-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled 13C5,15N4-agmatine (synthesized by decarboxylation of uniformly labeled 13C6,15N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,l,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1 % (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients. PMID:25957842

Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.

Science.gov (United States)

Dalluge, Joseph J; McCurtain, Jennifer L; Gilbertsen, Adam J; Kalstabakken, Kyle A; Williams, Bryan J

2015-07-01

A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1% (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients.

MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells | Office of Cancer Genomics