scholarly journals Reduction of In Vivo Placental Amino Acid Transport Precedes the Development of Intrauterine Growth Restriction in the Non-Human Primate

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2892
Author(s):  
Fredrick J. Rosario ◽  
Anita Kramer ◽  
Cun Li ◽  
Henry L. Galan ◽  
Theresa L. Powell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Acid Transport ◽  
Mole Percent ◽  
System A ◽  
System L ◽  
Human Primate

Intrauterine growth restriction (IUGR) is associated with reduced placental amino acid transport (AAT). However, it remains to be established if changes in AAT contribute to restricted fetal growth. We hypothesized that reduced in vivo placental AAT precedes the development of IUGR in baboons with maternal nutrient restriction (MNR). Baboons were fed either a control (ad libitum) or MNR diet (70% of control diet) from gestational day (GD) 30. At GD 140, in vivo transplacental AA transport was measured by infusing nine (13)C- or (2)H-labeled essential amino acids (EAAs) as a bolus into the maternal circulation at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each EAA was measured. Microvillous plasma membrane (MVM) system A and system L transport activity were determined. Fetal and placental weights were not significantly different between MNR and control. In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly decreased for tryptophan in MNR. MVM system A and system L activity was markedly reduced in MNR. Reduction of in vivo placental amino acid transport precedes fetal growth restriction in the non-human primate, suggesting that reduced placental amino acid transfer may contribute to IUGR.

scholarly journals A rapid method for the functional reconstitution of amino acid transport systems from rat liver plasma membranes. Partial purification of System A

1988 ◽  
Vol 255 (3) ◽  
pp. 963-969 ◽  
Author(s):  
A R Quesada ◽  
J D McGivan
Keyword(s):  
Amino Acid ◽  
Rapid Method ◽  
Amino Acid Transport ◽  
Plasma Membranes ◽  
Transport Systems ◽  
Partial Purification ◽  
Acid Transport ◽  
Transport Activity ◽  
System A ◽  
System L

A rapid method for the functional reconstruction of amino acid transport from liver plasma-membrane vesicles using the neutral detergent decanoyl-N-glucamide (‘MEGA-10’) is described. The method is a modification of that previously employed in this laboratory for reconstitution of amino acid transport systems from kidney brush-border membranes [Lynch & McGivan (1987) Biochem. J. 244, 503-508]. The transport activities termed ‘System A’, ‘System N’, and ‘System L’ are all reconstituted. The reconstitution procedure is rapid and efficient and is suitable as an assay for transport activity in studies involving membrane fractionation. By using this reconstitution procedure, System A transport activity was partially purified by lectin-affinity chromatography.

scholarly journals Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon

2015 ◽  
Vol 309 (7) ◽  
pp. R740-R746 ◽  
Author(s):  
Priyadarshini Pantham ◽  
Fredrick J. Rosario ◽  
Mark Nijland ◽  
Alex Cheung ◽  
Peter W. Nathanielsz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fetal Growth ◽  
Control Diet ◽  
Later Life ◽  
Nutrient Restriction ◽  
Mole Percent ◽  
Maternal Undernutrition ◽  
System A ◽  
System L

Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood. We hypothesized that MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplacental transfer of AAs. Pregnant baboons were fed either a control (ad libitum, n = 7), or MNR diet (70% of control diet, n = 7) from gestational day (GD) 30. At GD 165 (0.9 gestation), placentas ( n = 7 in each group) were collected, and microvillous plasma membrane vesicles (MVM) isolated. MVM system A and system L AA transport was determined in vitro using radiolabeled substrates and rapid filtration techniques. In vivo transplacental AA transport was assessed by infusing nine 13C- or 2H-labeled essential AA as a bolus into the maternal circulation ( n = 5 control, n = 4 MNR) at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each essential AA was calculated. Fetal and placental weights were significantly reduced in the MNR group compared with controls ( P < 0.01). The activity of system A and system L was markedly reduced by 73 and 84%, respectively, in MVM isolated from baboon placentas at GD 165 following MNR ( P < 0.01). In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly reduced for leucine, isoleucine, methionine, phenylalanine, threonine, and tryptophan in MNR baboons ( P < 0.05). This is the first study to investigate placental AA transport in a nonhuman primate model of MNR. We demonstrate that the downregulation of system A and system L activity in syncytiotrophoblast MVM in MNR leads to decreased transplacental AA transport and, consequently, reduced circulating fetal AA concentrations, a potential mechanism linking maternal undernutrition to reduced fetal growth.

Biodistribution of [11C]methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo

2001 ◽  
Vol 28 (7) ◽  
pp. 847-854 ◽  
Author(s):  
Eija Sutinen ◽  
Sirkku Jyrkkiö ◽  
Tove Grönroos ◽  
Merja Haaparanta ◽  
Pertti Lehikoinen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
System A

Neutral amino acid transport by isolated small intestinal cells from guinea pigs

1991 ◽  
Vol 261 (6) ◽  
pp. G1030-G1036 ◽  
Author(s):  
J. R. Del Castillo ◽  
R. Muniz
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Incubation Medium ◽  
Isobutyric Acid ◽  
Neutral Amino Acid ◽  
Acid Transport ◽  
Independent System ◽  
Isolated Enterocytes ◽  
System A ◽  
System L

Neutral amino acid transport was examined by using isolated enterocytes. Cells transport L-alanine by at least three different mechanisms: two Na(+)-dependent systems (A and ASC) and one Na(+)-independent mechanism (system L), in addition to passive entry. System A was characterized acterized by measuring the Na(+)-dependent alpha-(methylamino)isobutyric acid (MeAIB) uptake. Na(+)-dependent MeAIB uptake was concentrative and saturable. Vmax was obtained at 80mM Na+ in the incubation medium and Kt app for Na+ was 21.5 mM. Kt app for MeAIB was 6.75 +/- 0.37 mM and the Vmax was 14.2 +/- 0.3 nmol.mg-1.min-1. System ASC was studied by evaluating the Na(+)-dependent L-alanine uptake, insensitive to MeAIB and inhibitable by L-serine and L-cysteine. Uptake by this mechanism was also concentrative and saturable. Maximal uptake was obtained with 80 mM Na+ in the incubation medium and Kt app for Na+ was 29.7 mM. Kt app for L-alanine was 7.02 +/- 0.61 mM and Vmax was 5.44 +/- 0.19 nmol.mg-1.min-1. The Na(+)-independent system L was studied by measuring cycloleucine uptake in Na(+)-free medium. It had a saturable and a nonsaturable component. Only the saturable component was concentrative; it was inhibited by 2-amino-2-norbornanecarboxylic acid and was capable of mediating exchange diffusion. Kt app for cycloleucine was 4.05 +/- 0.72 mM and the Vmax was 31.9 +/- 1.3 nmol.mg-1.min-1. These results confirm the existence of Na(+)-dependent systems A and ASC and Na(+)-independent system L in isolated enterocytes.

Inactivation of amino acid transport in rat hepatocytes and hepatoma cells by PCMBS

1988 ◽  
Vol 255 (3) ◽  
pp. C340-C345 ◽  
Author(s):  
T. C. Chiles ◽  
K. L. Dudeck-Collart ◽  
M. S. Kilberg
Keyword(s):  
Amino Acid ◽  
Amino Acid Transport ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Hepatoma Cells ◽  
Transport Systems ◽  
Acid Transport ◽  
System A ◽  
System L ◽  
Normal Rat

the transport of amino acids by both normal rat hepatocytes and rat H4 hepatoma cells has been tested for inactivation by sulfhydryl-preferring, protein-modifying reagents. Amino acid transport by systems A, ASC, N, L, and y+ in the H4 hepatoma cells was relatively resistant to inactivation by the alkylating reagent N-ethylmaleimide (NEM), whereas uptake mediated by systems A, ASC, and L was decreased in normal rat hepatocytes. In contrast, nearly all of the amino acid transport systems in both cell types were inhibited strongly by p-chloromercuribenzene sulfonate (PCMBS). The exceptions were the H4 hepatoma system y+ activity (72% of control) and system L-mediated uptake (121% of control) in normal hepatocytes. Although transport via system A was equally sensitive to inhibition by PCMBS in both cell types, substrate-dependent protection from this inactivation was observed only in the H4 hepatoma cells. These results illustrate the significant differences that exist between normal and transformed liver cells in respect to amino acid transport inactivation by sulfhydryl reagents.

Leucine activates system A amino acid transport in L6 rat skeletal muscle cells

1995 ◽  
Vol 269 (5) ◽  
pp. C1287-C1294 ◽  
Author(s):  
H. E. McDowell ◽  
G. R. Christie ◽  
G. Stenhouse ◽  
H. S. Hundal
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Second Phase ◽  
Acid Transport ◽  
Rat Skeletal Muscle ◽  
Gene Encoding ◽  
System A ◽  
System L ◽  
Igf I

In this study, we present evidence showing that leucine is involved in the upregulation of system A amino acid transport activity in the L6 rat skeletal muscle cell line. At leucine concentrations of > or = 0.05 mM, the uptake of N-methylamino-alpha-isobutyric acid (MeAIB), a paradigm system A substrate, was stimulated by up to 50%. Kinetic analysis revealed that this stimulation was a result of an increase in the maximal transport rate of MeAIB uptake, from 327 +/- 26 to 450 +/- 8 pmol.min-1.mg protein-1 after incubation of cells with leucine. No significant change in the concentration at which MeAIB transport was half maximal was observed. System A activation was biphasic, reaching an initial plateau after 3 h, with a second phase of activation being observed after 5 h. The initial activation of system A transport occurred by a mechanism distinct from that activated by insulin-like growth factor-I (IGF-I) (3 nM), since the effects of leucine and IGF-I were additive. This activation was not due to transstimulation, since 2-amino-2-norbornane-carboxylic acid, a specific system L substrate, did not stimulate system A. Leucine's keto acid, ketoisocaproic acid, prevented the activation of system A transport, whereas aminooxyacetate, a transaminase inhibitor, augmented the increase in system A activity by leucine. Both cycloheximide and actinomycin D inhibited the leucine-induced increase in MeAIB uptake. The present results indicate that leucine, or some cellular component regulated by it, is capable of stimulating system A transport through control of DNA transcription, possibly of a gene encoding either a repressor or enhancer molecule of system A or perhaps of the gene encoding system A itself.

scholarly journals Glucocorticoid regulation of amino acid transport in primary human trophoblast cells

2019 ◽  
Vol 63 (4) ◽  
pp. 239-248 ◽  
Author(s):  
O.R. Vaughan ◽  
T.L. Powell ◽  
T. Jansson
Keyword(s):  
Amino Acid ◽  
Insulin Receptor ◽  
Amino Acid Transport ◽  
Mtor Signaling ◽  
Acid Uptake ◽  
Protein Abundance ◽  
Acid Transport ◽  
Human Trophoblast ◽  
System A ◽  
System L

Excess maternal glucocorticoids reduce placental amino acid transport and fetal growth, but whether these effects are mediated directly on the syncytiotrophoblast remains unknown. We hypothesised that glucocorticoids inhibit mechanistic target of rapamycin (mTOR) signaling and insulin-stimulated System A amino acid transport activity in primary human trophoblast (PHT) cells. Syncytialised PHTs, isolated from term placentas (n = 15), were treated with either cortisol (1 μM) or dexamethasone (1 μM), ± insulin (1 nM) for 24 h. Compared to vehicle, dexamethasone increased mRNA expression, but not protein abundance of the mTOR suppressor, regulated in development and DNA damage response 1 (REDD1). Dexamethasone enhanced insulin receptor abundance, activated mTOR complex 1 and 2 signaling and stimulated System A activity, measured by Na+-dependent 14C-methylaminoisobutyric acid uptake. Cortisol also activated mTORC1 without significantly altering insulin receptor or mTORC2 read-outs or System A activity. Both glucocorticoids downregulated expression of the glucocorticoid receptor and the System A transporter genes SLC38A1, SLC38A2 and SLC38A4, without altering SNAT1 or SNAT4 protein abundance. Neither cortisol nor dexamethasone affected System L amino acid transport. Insulin further enhanced mTOR and System A activity, irrespective of glucocorticoid treatment and despite downregulating its own receptor. Contrary to our hypothesis, glucocorticoids do not inhibit mTOR signaling or cause insulin resistance in cultured PHT cells. We speculate that glucocorticoids stimulate System A activity in PHT cells by activating mTOR signaling, which regulates amino acid transporters post-translationally. We conclude that downregulation of placental nutrient transport in vivo following excess maternal glucocorticoids is not mediated by a direct effect on the placenta.

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