Placental Amino Acid Uptake. II. Tissue Preincubation, Fluid Distribution, and Mechanisms of Regulation

Smith, Carl H.; Depper, Rosalyn

doi:10.1203/00006450-197407000-00002

Cited by 56 publications

(21 citation statements)

References 9 publications

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“…System A is regulated by substrate availability. Depletion of system A substrates leads to an increase in transporter activity when substrates become available again (Smith and Depper, 1974). This response is known as adaptive regulation and is perhaps the most understood mechanism of system A regulation.…”

Section: Regulation Of System a By External Factorsmentioning

confidence: 99%

“…System A is also trans-inhibited i.e. high intracellular concentrations of it own substrates can lead to reduced activity (Smith and Depper, 1974). The nutritional status of the mother during pregnancy could impact on substrate availability for system A, for example in teenage pregnancies where maternal diet is poor, or in overweight and obese mothers where substrate availability may be increased.…”

Section: Regulation Of System a By External Factorsmentioning

confidence: 99%

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Placental nutrient supply and fetal growth

Desforges¹,

Sibley²

2010

Int. J. Dev. Biol.

145

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This review considers mechanisms by which transfer across the placenta takes place and how the capacity of the placenta to supply nutrients relates to fetal growth and vice versa. Blood flow through both uterine and umbilical circulations of the placenta, the structural properties of the placental exchange barrier and its related diffusional permeability, and the expression and activity of a wide range of transporter proteins in the syncytiotrophoblast, the transporting epithelium of the placenta, all need to be taken into account in considering placental supply capacity. We discuss the evidence that each of these factors affects, and is affected by, fetal growth rate and consider the regulatory mechanisms involved, with a particular focus on data that has emerged from study of the system A amino acid transporter. We consider that future work will build on the considerable foundation of knowledge regarding placental transfer mechanisms, as well as the other aspects of placental structure and function, to develop new diagnostic and therapeutic strategies for pregnancy complications, such as fetal growth restriction or overgrowth.

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Section: Regulation Of System a By External Factorsmentioning

confidence: 99%

Section: Regulation Of System a By External Factorsmentioning

confidence: 99%

Placental nutrient supply and fetal growth

Desforges¹,

Sibley²

2010

Int. J. Dev. Biol.

145

View full text Add to dashboard Cite

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“…Smith & Depper (1974) suggested that system A in the placenta may be regulated by substrate but these data did not examine protein or gene expression. The transporters for placental taurine uptake show a substrate-specific adaptive response involving both transcriptional and post-transcriptional events in taurinedeprived JAR cells (Jayanthi et al 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Smith & Depper 1974). Trans-placental transfer of a-aminoisobytyric acid (AIB), leucine and lysine has been demonstrated in human (Schneider et al 1987) and guinea pig (Carstensen & Leichtweiss 1986, Wheeler & Yudilevich 1989 placentas.…”

Section: Introductionmentioning

confidence: 99%

“…Its effectors include pH, cell volume (Ruiz-Montasell et al 1994) and a variety of hormones such as insulin (McDowell et al 1998), glucagon (Yao et al 2000) and insulin-like growth factor-I (Karl 1995). Amino acid availability has also been shown to regulate system A function in several cell types including hepatocytes (Bracy et al 1986) and placental fragments (Smith & Depper 1974), and SNAT2 undergoes the process of 'adaptive regulation' in C6 glioma cells (Ling et al 2001), L6 myotubes and adipocytes (Hyde et al 2001) when incubated in amino acid-free medium. This response, which mirrors the effect on actual transport of system A substrates, involves two phases.…”

Section: Introductionmentioning

confidence: 99%

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Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

Jones¹,

Ashworth²,

Page³

et al. 2006

Reproduction

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Trans-placental transport of amino acids is vital for the developing fetus. Using the BeWo cell line as a placental model, we investigated the effect of restricting amino acid availability on amino acid transport system type A. BeWo cells were cultured either in amino acid-depleted (without non-essential amino acids) or control media for 1, 3, 5 or 6 h. System A function was analysed using a(methyl-amino)isobutyric acid (MeAIB) transcellular transport studies. Transporter (sodium coupled neutral amino acid transporter (SNAT1/2)) expression was analysed at mRNA and protein level by Northern and Western blotting respectively. Localisation was carried out using immunocytochemistry. MeAIB transcellular transport was significantly (P < 0.05) increased by incubation of the cells in amino acid-depleted medium for 1 h, and longer incubation times caused further increases in the rate of transfer. However, the initial response was not accompanied by an increase in SNAT2 mRNA; this occurred only after 3 h and further increased for the rest of the 6-h incubation. Similarly, it took several hours for a significant increase in SNAT2 protein expression. In contrast, relocalisation of existing SNAT2 transporters occurred within 30 min of amino acid restriction and continued throughout the 6-h incubation. When the cells were incubated in medium with even lower amino acid levels (without non-essential plus 0.5 3 essential amino acids), SNAT2 mRNA levels showed further significant (P < 0.0001) up-regulation. However, incubation of cells in depleted medium for 6 h caused a significant (P 5 0.014) decrease in the expression of SNAT1 mRNA. System L type amino acid transporter 2 (LAT2) expression was not changed by amino acid restriction, indicating that the responses seen in the system A transporters were not a general cell response. These data have shown that placental cells adapt in vitro to nutritional stress and have identified the physiological, biochemical and genomic mechanisms involved. Reproduction (2006) 131 951-960

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