Search results for "Amino acid transporter"
showing 10 items of 45 documents
Neuroprotective effect of ceftriaxone on the penumbra in a rat venous ischemia model.
2012
Glutamate transporter-1 (GLT-1) maintains low concentrations of extracellular glutamate by removing glutamate from the extracellular space. It is controversial, however, whether upregulation of GLT-1 is neuroprotective under all ischemic/hypoxic conditions. Recently, a neuroprotective effect of preconditioning with a β-lactam antibiotic ceftriaxone (CTX) that increases expression of GLT-1 has been reported in animal models of focal ischemia. On the other hand, it is said that CTX does not play a neuroprotective role in an in vitro study. Thus, we examined the effect of CTX on ischemic injury in a rat model of two-vein occlusion (2VO). This model mimics venous ischemia during, e.g. tumor sur…
Does parental expressed emotion moderate genetic effects in ADHD? An exploration using a genome wide association scan.
2008
Contains fulltext : 70497.pdf (Publisher’s version ) (Closed access) Studies of gene x environment (G x E) interaction in ADHD have previously focused on known risk genes for ADHD and environmentally mediated biological risk. Here we use G x E analysis in the context of a genome-wide association scan to identify novel genes whose effects on ADHD symptoms and comorbid conduct disorder are moderated by high maternal expressed emotion (EE). SNPs (600,000) were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. ADHD symptom severity and comorbid conduct disorder was measured using the Parental Account of Ch…
Differential cystine and dibasic amino acid handling after loss of function of the amino acid transporter b0,+ AT (Slc7a9) in mice
2013
Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 ( rBAT) and SLC7A9 ( b 0,+ AT). Gene targeting of the catalytic subunit ( Slc7a9) in mice leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here, we studied this non-type I cystinuria mouse model using gene expression analysis, Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake experiments to further characterize the renal and intestinal consequences of losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine suggested that arginine and ornithine are transported via other routes apart from system b0,+. No remarkable gene expression changes were…
Rôle du transporteur d'acides aminés Minidiscs dans le fonctionnement du système nerveux chez Drosophila melanogaster
2015
Amino acids have many functions in the body in addition to their role as basic constituents of proteins. They can for example serve as a neurotransmitter or signal for the activation of intracellular pathways. Carriers of the SLC protein family facilitate their path through the plasma membrane. The heterodimeric amino acid transporters HAT belong to SLC proteins. HAT are composed of a light chain SLC7 ensuring the specificity of transport and a heavy chain SLC3 involved in the addressing of the protein complex to the plasma membrane. My thesis focused on studying the role of a SLC7 homologue in drosophila, Minidiscs (Mnd), in the functioning of the nervous system. Mnd might belong to system…
Intracellular accumulation of l-Arg, kinetics of transport, and potassium leak conductance in oocytes from Xenopus laevis expressing hCAT-1, hCAT-2A,…
2004
AbstractCationic amino acid transporters play an important role in the intracellular supply of l-Arg and the generation of nitric oxide. Since the transport of l-Arg is voltage-dependent, we aimed at determining the intracellular l-Arg concentration and describing the transport of l-Arg in terms of Michaelis–Menten kinetics, taking into account membrane voltage. The human isoforms of the cationic amino acid transporters, hCAT-1, hCAT-2A, and hCAT-2B, were expressed in oocytes from Xenopus laevis and studied with the voltage clamp technique and in tracer experiments. We found that l-Arg was concentrated intracellularly by all hCAT isoforms and that influx and efflux, in the steady state of e…
The transport activity of the human cationic amino acid transporter hCAT-1 is downregulated by activation of protein kinase C
2001
1 The human cationic amino acid transporter hCAT-1 contains several consensus sequences for phosphorylation by protein kinase C (PKC). This study investigates the eAect of PKC activation on hCAT-1-mediated transport. 2 When expressed in Xenopus laevis oocytes, hCAT-1-mediated L-arginine transport was reduced to 44+3% after a 30 min treatment of the oocytes with 100 nM phorbol-12-myristate-13-acetate (PMA). 4a-phorbol-12,13-didecanoate (4a-PDD, 100 nM) had no eAect. 3 In EA.hy926 endothelial cells, maximal inhibition of hCAT-1-mediated L-arginine transport (to 3‐11% of control) was observed after treatment of the cells with 100 nM PMA for 4 h. A 20‐30 h exposure of the cells to 100 nM PMA le…
Inhibition of nitric oxide synthase abrogates lipopolysaccharides-induced up-regulation of L-arginine uptake in rat alveolar macrophages
2001
It was tested whether the inducible nitric oxide synthase (iNOS) pathway might be involved in lipopolysaccharides-(LPS)-induced up-regulation of L-arginine transport in rat alveolar macrophages (AM). AM were cultured in absence or presence of LPS. Nitrite accumulation was determined in culture media and cells were used to study [3H]-L-arginine uptake or to isolate RNA for RT - PCR. Culture in presence of LPS (1 microg ml(-1), 20 h) caused 11 fold increase of nitrite accumulation and 2.5 fold increase of [3H]-L-arginine uptake. The inducible NO synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) present alone during culture had only marginal effects on [3H]-L-arginin…
Two amino acid residues determine the low substrate affinity of human cationic amino acid transporter-2A.
2003
Mammalian cationic amino acid transporters (CAT) differ in their substrate affinity and sensitivity to trans-stimulation. The apparent Km values for cationic amino acids and the sensitivity to trans-stimulation of CAT-1, -2B, and -3 are characteristic of system y+. In contrast, CAT-2A exhibits a 10-fold lower substrate affinity and is largely independent of substrate at the trans-side of the membrane. CAT-2A and -2B demonstrate such divergent transport properties, even though their amino acid sequences differ only in a stretch of 42 amino acids. Here, we identify two amino acid residues within this 42-amino acid domain of the human CAT-2A protein that are responsible for the apparent low af…
Paradoxical effect of l-arginine: Acceleration of endothelial cell senescence
2009
We have recently shown that inhibition of nitric oxide (NO) synthesis by asymmetrical dimethylarginine (ADMA) accelerated endothelial cell (EC) senescence which was prevented by coincubation with L-arginine; however the effect of long-term treatment of l-arginine alone on senescence of ECs have not been investigated. Human ECs were cultured in medium containing different concentrations of L-arginine until senescence. L-Arginine paradoxically accelerated senescence indicated by inhibiting telomerase activity. Moreover, L-arginine decreased NO metabolites, increased peroxynitrite, and 8-iso-prostaglandin F(2alpha) formation. In old cells, the mRNA expression of human amino acid transporter (h…
[68Ga]Ga-DO2A-(OBu-l-tyr)2: Synthesis, 68Ga-radiolabeling and in vitro studies of a novel 68Ga-DO2A-tyrosine conjugate as potential tumor tracer for …
2009
The synthesis, (68)Ga-labeling and in vitro study of the novel tyrosine chelate derivative [(68)Ga]Ga-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid-4,10-di-(O-butyl)-l-tyrosine ([(68)Ga]Ga-DO(2)A-(OBu-l-tyr)(2)) as a potential tracer for imaging tumor metabolism by positron emission tomography (PET) is presented. This approach combines the biological amino acid transporter targeting properties of l-tyrosine with the outstanding availability of (68)Ga(III) via the (68)Ge/(68)Ga generator. In vitro studies utilizing the F98-glioblastoma cell line revealed specific uptake of [(68)Ga]Ga-DO2A-(OBu-l-tyr)(2) that was comparable to that of the reference O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET)…