Search results for "arginine"

Induced arginine transport via cationic amino acid transporter-1 is necessary for human T-cell proliferation

2015

Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor-associated arginine deprivation, mainly induced by myeloid-derived suppressor cells, is a central mechanism of tumor immune escape from T-cell-mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T-cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naive and memory CD4(+) T cells as well as CD8(+) T cells specifically upregulated the hum…

Reconstitution of T Cell Proliferation under Arginine Limitation: Activated Human T Cells Take Up Citrulline via L-Type Amino Acid Transporter 1 and …

2017

In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological anti-tumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL). Here we demonstrate that anti-CD3/anti-CD28-activated human primary CD4+ and CD8+ T c…

Uncoupling of eNOS in Cardiovascular Disease

2017

Abstract Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) represents a key vasoprotective factor. Under conditions of cardiovascular diseases, such as hypertension, diabetes, and atherosclerosis, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential cofactor for the eNOS enzyme, and deficiency of l -arginine, the eNOS substrate, and/or eNOS S-glutathionylation. Reversal of eNOS uncoupling may represent a novel therapeutic strategy for the prevention …

2015

Background Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. Methods 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. Results The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients wit…

Integration of polyamins in the cold acclimation response

2011

8 páginas, 1 figura, 3 tablas -- PAGS nros. 31-38

Pharmacological Interventions on Asymmetric Dimethylarginine, a Clinical Marker of Vascular Disease

2011

The aim of this paper is to review the latest data on the pharmacological modulation of asymmetric dimethylarginine in human disease. When the terminal nitrogens of the guanidine portion of an arginine become methylated through the action of N-methyl transferases, two chemically close, but physiologically different amino acids are synthesized: symmetric and asymmetric dimethylarginine. The vascular origin of asymmetric dimethylarginine and its inhibitory activity on endothelial nitric oxide synthase give it an important role in certain diseases in which microcirculation is compromised: hypertension, atherosclerosis, inflammatory bowel disease, and diabetes. This review discusses the role th…

Impairment of the extrusion transporter for asymmetric dimethyl-L-arginine: a novel mechanism underlying vasospastic angina.

2012

Abstract A 37-year old male patient presented with frequent angina attacks (up to 40/day) largely resistant to classical vasodilator therapy. The patient showed severe coronary and peripheral endothelial dysfunction, increased platelet aggregation and increased platelet-derived superoxide production. The endothelial nitric oxide synthase (eNOS)-inhibitor N G -nitro- l -arginine methyl ester (L-NAME) reduced superoxide formation in platelets identifying “uncoupled” eNOS as a superoxide source. Oral l -arginine normalized coronary and peripheral endothelial dysfunction and reduced platelet aggregation and eNOS-derived superoxide production. Plasma concentrations of the endogenous NOS inhibito…

Metabolomic Changes after Coffee Consumption: New Paths on the Block

2021

Scope Several studies suggest that regular coffee consumption may help preventing chronic diseases, but the impact of daily intake and the contribution of coffee metabolites in disease prevention are still unclear. The present study aimed at evaluating whether and how different patterns of coffee intake (one cup of espresso coffee/day, three cups of espresso coffee/day, one cup of espresso coffee/day and two cocoa-based products containing coffee two times per day) might impact endogenous molecular pathways. Methods and results A three-arm, randomized, cross-over trial was performed in 21 healthy volunteers who consumed each treatment for one month. Urine samples were collected to perform u…

Observations of time-based measures of flow-mediated dilation of forearm conduit arteries: implications for the accurate assessment of endothelial fu…

2010

Endothelium-dependent flow-mediated dilation (FMD) is measured as the increase in diameter of a conduit artery in response to reactive hyperemia, assessed either at a fixed time point [usually 60-s post-cuff deflation (FMD60)] or as the maximal dilation during a 5-min continuous, ECG-gated, measurement (FMDmax-cont). Preliminary evidence suggests that the time between reactive hyperemia and peak dilation (time to FMDmax) may provide an additional index of endothelial health. We measured FMDmax-cont, FMD60, and time to FMDmax in 30 young healthy volunteers, 22 healthy middle-aged adults, 16 smokers, 23 patients with hypertension, 40 patients with coronary artery disease, and 22 patients wit…

V2-receptor–mediated relaxation of human renal arteries in response to desmopressin

1999

The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and …