scholarly journals Reduced Na + K + ‐ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged ex vivo amino acid transporter activity

2020 ◽  
Vol 598 (8) ◽  
pp. 1625-1639 ◽  
Author(s):  
Jane Stremming ◽  
Thomas Jansson ◽  
Theresa L Powell ◽  
Paul J Rozance ◽  
Laura D Brown
Keyword(s):  
Amino Acid ◽  
Atpase Activity ◽  
Ex Vivo ◽  
Amino Acid Uptake ◽  
Amino Acid Transporter ◽  
Acid Uptake ◽  
Fetal Sheep ◽  
Intrauterine Growth ◽  
Acid Transporter ◽  
Sheep Muscle

scholarly journals Prolonged amino acid infusion into intrauterine growth-restricted fetal sheep increases leucine oxidation rates

2018 ◽  
Vol 315 (6) ◽  
pp. E1143-E1153 ◽  
Author(s):  
Sandra G. Wai ◽  
Paul J. Rozance ◽  
Stephanie R. Wesolowski ◽  
William W. Hay ◽  
Laura D. Brown
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Intrauterine Growth ◽  
Leucine Oxidation ◽  
Fetal Plasma ◽  
Oxidation Rates

Overcoming impaired growth in an intrauterine growth-restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We subjected fetal sheep to chronic placental insufficiency and tested whether prolonged amino acid infusion would increase protein accretion in these IUGR fetuses. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg−1·day−1 (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in the IUGR-AA than IUGR-Sal group ( P < 0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were fourfold higher in the IUGR-AA group ( P < 0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus the total amino acid delivery rate (net umbilical amino acid uptake + infusion rate) was higher in the IUGR-AA than IUGR-Sal group (30 ± 4 vs. 19 ± 1 μmol·kg−1·min−1, P < 0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate, measured using a leucine tracer, was higher in the IUGR-AA than IUGR-Sal group (2.5 ± 0.3 vs. 1.7 ± 0.3 μmol·kg−1·min−1, P < 0.05). Fetal protein accretion rate was not statistically different between the IUGR groups (1.6 ± 0.4 and 0.8 ± 0.3 μmol·kg−1·min−1 in IUGR-AA and IUGR-Sal, respectively) due to variability in response to amino acids. Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.

scholarly journals The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in Cancer

2018 ◽  
Vol 19 (8) ◽  
pp. 2373 ◽  
Author(s):  
Travis Salisbury ◽  
Subha Arthur
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Cells ◽  
Amino Acid Uptake ◽  
Essential Amino Acids ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Cancer Pathways ◽  
Acid Transporter

The progression of cancer is associated with increases in amino acid uptake by cancer cells. Upon their entry into cells through specific transporters, exogenous amino acids are used to synthesize proteins, nucleic acids and lipids and to generate ATP. The essential amino acid leucine is also important for maintaining cancer-associated signaling pathways. By upregulating amino acid transporters, cancer cells gain greater access to exogenous amino acids to support chronic proliferation, maintain metabolic pathways, and to enhance certain signal transduction pathways. Suppressing cancer growth by targeting amino acid transporters will require an in-depth understanding of how cancer cells acquire amino acids, in particular, the transporters involved and which cancer pathways are most sensitive to amino acid deprivation. L-Type Amino Acid Transporter 1 (LAT1) mediates the uptake of essential amino acids and its expression is upregulated during the progression of several cancers. We will review the upstream regulators of LAT1 and the downstream effects caused by the overexpression of LAT1 in cancer cells.

scholarly journals Leptin Stimulates the Activity of the System A Amino Acid Transporter in Human Placental Villous Fragments

2003 ◽  
Vol 88 (3) ◽  
pp. 1205-1211 ◽  
Author(s):  
N. Jansson ◽  
S. L. Greenwood ◽  
B. R. Johansson ◽  
T. L. Powell ◽  
T. Jansson
Keyword(s):  
Electron Microscopy ◽  
Amino Acid ◽  
Hormonal Regulation ◽  
Experimental System ◽  
Amino Acid Uptake ◽  
Amino Acid Transporter ◽  
Acid Uptake ◽  
Hormone Production ◽  
System A ◽  
Acid Transporter

The activity and expression of placental nutrient transporters are primary determinants for the supply of nutrients to the fetus, and these nutrients in turn regulate fetal growth. We developed an experimental system to assess amino acid uptake in single primary villous fragments to study hormonal regulation of the amino acid transporter system A in term human placenta. Validation of the method, using electron microscopy and studies of hormone production, indicated that fragments maintained ultrastructural and functional integrity for at least 3 h. The activity of system A was measured as the Na+-dependent uptake of methylaminoisobutyric acid (MeAIB), and the effect of 1 h incubation in various hormones was investigated. Uptake of MeAIB into villous fragments in the presence of Na+ was linear up to at least 30 min. Insulin (300 ng/ml, n = 14) increased system A activity by 56% (P &lt; 0.05). This effect was also present at insulin concentrations in the physiological range (+47% at 0.6 ng/ml, n = 10, P &lt; 0.05). Leptin (500 ng/ml, n = 14) increased Na+-dependent MeAIB uptake by 37% (P &lt; 0.05). System A activity increased in a concentration-dependent fashion in response to leptin (n = 10). However, neither epidermal GF (600 ng/ml), cortisol (340 ng/ml), nor GH (500 ng/ml) altered system A activity significantly (n = 14). We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter.

scholarly journals The Amino Acid-mTORC1 Pathway Mediates APEC TW-XM-Induced Inflammation in bEnd.3 Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9245
Author(s):  
Dong Zhang ◽  
Shu Xu ◽  
Yiting Wang ◽  
Peng Bin ◽  
Guoqiang Zhu
Keyword(s):  
Amino Acid ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Excitatory Amino Acid ◽  
Amino Acid Uptake ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Mtorc1 Pathway ◽  
Acid Transporter

The blood–brain barrier (BBB) is key to establishing and maintaining homeostasis in the central nervous system (CNS); meningitis bacterial infection can disrupt the integrity of BBB by inducing an inflammatory response. The changes in the cerebral uptake of amino acids may contribute to inflammatory response during infection and were accompanied by high expression of amino acid transporters leading to increased amino acid uptake. However, it is unclear whether amino acid uptake is changed and how to affect inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells in response to Avian Pathogenic Escherichia coli TW-XM (APEC XM) infection. Here, we firstly found that APEC XM infection could induce serine (Ser) and glutamate (Glu) transport from extracellular into intracellular in bEnd.3 cells. Meanwhile, we also shown that the expression sodium-dependent neutral amino acid transporter 2 (SNAT2) for Ser and excitatory amino acid transporter 4 (EAAT4) for Glu was also significantly elevated during infection. Then, in amino acid deficiency or supplementation medium, we found that Ser or Glu transport were involving in increasing SNAT2 or EAAT4 expression, mTORC1 (mechanistic target of rapamycin complex 1) activation and inflammation, respectively. Of note, Ser or Glu transport were inhibited after SNAT2 silencing or EAAT4 silencing, resulting in inhibition of mTORC1 pathway activation, and inflammation compared with the APEC XM infection group. Moreover, pEGFP-SNAT2 overexpression and pEGFP-EAAT4 overexpression in bEnd.3 cells all could promote amino acid uptake, activation of the mTORC1 pathway and inflammation during infection. We further found mTORC1 silencing could inhibit inflammation, the expression of SNAT2 and EAAT4, and amino acid uptake. Taken together, our results demonstrated that APEC TW-XM infection can induce Ser or Glu uptake depending on amino acid transporters transportation, and then activate amino acid-mTORC1 pathway to induce inflammation in bEnd.3 cells.

scholarly journals Identification and Characterization of Inhibitors of a Neutral Amino Acid Transporter, SLC6A19, Using Two Functional Cell-Based Assays

2018 ◽  
Vol 24 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Sanjay J. Danthi ◽  
Beirong Liang ◽  
Oanh Smicker ◽  
Benjamin Coupland ◽  
Jill Gregory ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Throughput Screening ◽  
Amino Acid Transporter ◽  
Neutral Amino Acid ◽  
Imaging Plate ◽  
Acid Uptake ◽  
Functional Assays ◽  
Neutral Amino Acid Transporter ◽  
Acid Transporter ◽  
Pharmacologically Active

SLC6A19 (B0AT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. A diverse collection of 3440 pharmacologically active compounds from the Microsource Spectrum and Tocriscreen collections were tested at 10 µM in both assays using MDCK cells stably expressing hSLC6A19 and its obligatory subunit, TMEM27. Compounds that inhibited SLC6A19 activity in both assays were further confirmed for activity and selectivity and characterized for potency in functional assays against hSLC6A19 and related transporters. A single compound, cinromide, was found to robustly, selectively, and reproducibly inhibit SLC6A19 in all functional assays. Structurally related analogs of cinromide were tested to demonstrate structure–activity relationship (SAR). The assays described here are suitable for carrying out high-throughput screening campaigns to identify modulators of SLC6A19.

scholarly journals Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats

2020 ◽  
Vol 21 (5) ◽  
pp. 1849
Author(s):  
Jie Xu ◽  
Jiao Wang ◽  
Yang Cao ◽  
Xiaotong Jia ◽  
Yujia Huang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rat Model ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Amino Acid Transport System ◽  
Intrauterine Growth ◽  
System L ◽  
Acid Transporter ◽  
Transporter Expression

Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placentas of streptozotocin-induced diabetic pregnant rats, which was associated with the decreased birthweight in the rats. A decreased placental efficiency and decreased placental mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity were also found in the rat model. In addition, hyperglycemia in vitro could inhibit amino acid transporter expression and mTORC1 activity in human trophoblast. Inhibition of mTORC1 activity led to reduced amino acid transporter expression in placental trophoblast. We concluded that reduced placental mTORC1 activity during pregnancy resulted in decreased placental amino acid transporter expression and, subsequently, contributed to fetal intrauterine growth restriction in pregnancies complicated with diabetes.

scholarly journals Effect of IGF-I on serine metabolism in fetal sheep

2000 ◽  
Vol 165 (2) ◽  
pp. 261-269 ◽  
Author(s):  
EC Jensen ◽  
P van Zijl ◽  
PC Evans ◽  
JE Harding
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Amino Acid Uptake ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Amino Acid Synthesis ◽  
Fetal Sheep ◽  
Igf I

Acute infusion of IGF-I to the fetus has been shown to inhibit amino acid oxidation and appears to increase fetoplacental amino acid uptake. This study was designed to investigate further the effects of IGF-I on fetal amino acid metabolism. Radiolabeled serine was used to test the hypothesis that fetal IGF-I infusion enhances serine uptake into the fetus and/or placenta and inhibits serine oxidation. Eight fetal sheep were studied at 127 days of gestation before and during a 4-h infusion of IGF-I (50 microg/h per kg). During the infusion there was no change in uptake of serine or its oxidation by fetus or placenta. However, both uptake and oxidation of serine and glycine decreased in the fetal carcass. There was also a decrease in fetal blood serine and glycine concentrations which could indicate a decrease in protein breakdown, although reduced amino acid synthesis cannot be excluded. Thus IGF-I appeared to influence the distribution of these amino acids as oxidative substrates between different fetal tissues. In addition, fetal IGF-I infusion increased the conversion of serine to glycine which is likely to have increased the availability of one-carbon groups for biosynthesis. Our data provide further evidence that IGF-I plays a role in the regulation of fetoplacental amino acid metabolism.

Effect of Exogenous Gangliosides on Amino Acid Uptake and Na+,K+-ATPase Activity in Superior Cervical and Nodose Ganglia of Rats

1987 ◽  
Vol 49 (1) ◽  
pp. 201-207 ◽  
Author(s):  
Yutaka Nagata ◽  
Masato Ando ◽  
Mitsuyoshi Iwata ◽  
Atsushi Hara ◽  
Tamotsu Taketomi
Keyword(s):  
Amino Acid ◽  
Atpase Activity ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Nodose Ganglia
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