L-arginine transport and nitric oxide synthesis in human endothelial progenitor cells

Díaz-Pérez, Francisca; Radojkovic, Claudia; Aguilera, Valeria; Veas, Carlos; González, Marcelo; Lamperti, Liliana; Escudero, Carlos; Aguayo, Claudio

doi:10.1097/fjc.0b013e318269ae2f

Cited by 16 publications

(5 citation statements)

References 43 publications

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“…In addition, kinetic data for L-arginine were determined to evaluate substrate-specific differences and as a positive control for comparison with published data. Previous studies investigating the uptake of L-arginine in native endothelial cells or macrophages were limited by the fact that these studies relied on endogenous expression of known and unknown membrane transporters and, thus, did not permit to assess the distinct kinetics of individual transporters (Diaz-Perez et al 2012;Closs et al 2000). High-affinity transport kinetics were mostly attributed to CAT1, but the possible contribution of lower affinity transporters resembling system y ?…”

Section: Discussionmentioning

confidence: 99%

Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1)

et al. 2013

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Asymmetric dimethylarginine (ADMA), inhibiting the nitric oxide (NO) synthesis from L-arginine, is a known cardiovascular risk factor. Our aim was to investigate if ADMA and/or L-arginine are substrates of the human cationic amino acid transporters 2A (CAT2A, SLC7A2A) and 2B (CAT2B, SLC7A2B), the organic cation transporter 2 (OCT2, SLC22A2), and the multidrug and toxin extrusion protein 1 (MATE1, SLC47A1). We systematically investigated the kinetics of ADMA and L-arginine transport in human embryonic kidney (HEK293) cells stably overexpressing CAT2A, CAT2B, OCT2, or MATE1. Vector-only transfected HEK293 cells served as controls. Compared to vector control cells, uptake of ADMA and L-arginine was significantly higher (p < 0.05) in cells expressing CAT2B and OCT2 at almost all investigated concentrations, while cells expressing CAT2A only showed a significant uptake at concentrations above 300 μM. Uptake of MATE1 overexpressing cells was significantly (p < 0.05) higher at pH 7.8 and 8.2 than controls. Apparent V max values (nmol mg protein(-1) min(-1)) for cellular uptake of ADMA and L-arginine were ≈11.8 ± 1.2 and 19.5 ± 0.7 for CAT2A, ≈14.3 ± 1.0 and 15.3 ± 0.4 for CAT2B, and 6.3 ± 0.3 and >50 for OCT2, respectively. Apparent K m values (μmol/l) for cellular uptake of ADMA and L-arginine were ≈3,033 ± 675 and 3,510 ± 419 for CAT2A, ≈4,021 ± 532 and 952 ± 92 for CAT2B, and 967 ± 143 and >10,000 for OCT2, respectively. ADMA and L-arginine are substrates of human CAT2A, CAT2B, OCT2 and MATE1. Transport kinetics of CAT2A, CAT2B, and OCT2 indicate a low affinity, high capacity transport, which may be relevant for renal and hepatic elimination of ADMA or L-arginine.

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Section: Discussionmentioning

confidence: 99%

Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1)

et al. 2013

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“…In several cell types, L-arginine transport has been considered as a rate limiting factor for NO synthesis. HUVECs, endothelial cells from human placental microvessels, human saphenous veins and human endothelial progenitor cells (hEPC) are all able to transport L-arginine and synthesize NO [129]. Emerging evidence suggests that upregulation of arginase is of central importance for reduced NO bioavailability due to competition for the substrate L-arginine between arginase and the eNOS.…”

Section: Arginasementioning

confidence: 99%

At the interface of antioxidant signalling and cellular function: Key polyphenol effects

Kerimi

Williamson

2016

Molecular Nutrition Food Res

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The hypothesis that dietary (poly)phenols promote well‐being by improving chronic disease‐risk biomarkers, such as endothelial dysfunction, chronic inflammation and plasma uric acid, is the subject of intense current research, involving human interventions studies, animal models and in vitro mechanistic work. The original claim that benefits were due to the direct antioxidant properties of (poly)phenols has been mostly superseded by detailed mechanistic studies on specific molecular targets. Nevertheless, many proposed mechanisms in vivo and in vitro are due to modulation of oxidative processes, often involving binding to specific proteins and effects on cell signalling. We review the molecular mechanisms for 3 actions of (poly)phenols on oxidative processes where there is evidence in vivo from human intervention or animal studies. (1) Effects of (poly) phenols on pathways of chronic inflammation leading to prevention of some of the damaging effects associated with the metabolic syndrome. (2) Interaction of (poly)phenols with endothelial cells and smooth muscle cells, leading to effects on blood pressure and endothelial dysfunction, and consequent reduction in cardiovascular disease risk. (3) The inhibition of xanthine oxidoreductase leading to modulation of intracellular superoxide and plasma uric acid, a risk factor for developing type 2 diabetes.

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Section: Resultsmentioning

confidence: 97%

“…These results indicate that the developed device can be used to monitor NO changes on different culture days by using the same sample. Moreover, the results are attributed to eNOS and cationic amino acid transporter 26 expression during cell maturation. Unfortunately, the effect of the stimulating substrates was not completely removed because of the bare Au electrode, which is disadvantageous.…”

Section: Fabrication Of Porous Au Membrane Electrodesmentioning

confidence: 95%

Vasculature-on-a-Chip with a Porous Membrane Electrode for In Situ Electrochemical Detection of Nitric Oxide Released from Endothelial Cells

Utagawa,

Ino,

Hiramoto

et al. 2023

Anal. Chem.

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L-arginine transport and nitric oxide synthesis in human endothelial progenitor cells

Cited by 16 publications

References 43 publications

Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1)

Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1)

At the interface of antioxidant signalling and cellular function: Key polyphenol effects

Vasculature-on-a-Chip with a Porous Membrane Electrode for In Situ Electrochemical Detection of Nitric Oxide Released from Endothelial Cells

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