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The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane.

Desforges M, Mynett KJ, Jones RL, Greenwood SL, Westwood M, Sibley CP, Glazier JD - J. Physiol. (Lond.) (2008)

Bottom Line: The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01).In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05).This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.

View Article: PubMed Central - PubMed

Affiliation: Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. michelle.desforges@manchester.ac.uk

ABSTRACT
Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.

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[14C] MeAIB uptake by placental villous fragmentsA, Na+-dependent [14C]MeAIB uptake by first trimester (FT) and term placental villous fragments (n= 16 in each group). These data represent system A-mediated transport of [14C]MeAIB and are presented as median and interquartile range. System A activity is significantly higher at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test). B, Na+-dependent [14C]MeAIB uptake by first trimester (n= 6) and term (n= 3) villous fragments in the presence of 5 mm MeAIB, representing SNAT4-mediated activity. SNAT4-mediated activity is significantly lower at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test).
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fig04: [14C] MeAIB uptake by placental villous fragmentsA, Na+-dependent [14C]MeAIB uptake by first trimester (FT) and term placental villous fragments (n= 16 in each group). These data represent system A-mediated transport of [14C]MeAIB and are presented as median and interquartile range. System A activity is significantly higher at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test). B, Na+-dependent [14C]MeAIB uptake by first trimester (n= 6) and term (n= 3) villous fragments in the presence of 5 mm MeAIB, representing SNAT4-mediated activity. SNAT4-mediated activity is significantly lower at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test).

Mentions: Figure 4A shows that Na+-dependent [14C]MeAIB uptake, representing system A-mediated transport, by term placental villous fragments is significantly higher than uptake by first trimester fragments. This increase could not be attributed to differences in fragment size (Greenwood & Sibley, 2006) as the protein content of first trimester and term placental villous fragments was comparable (mean ±s.e.m.= 501.8 ± 46.3 and 625.7 ± 45.6 μg, respectively, unpaired t test, P= 0.07).


The SNAT4 isoform of the system A amino acid transporter is functional in human placental microvillous plasma membrane.

Desforges M, Mynett KJ, Jones RL, Greenwood SL, Westwood M, Sibley CP, Glazier JD - J. Physiol. (Lond.) (2008)

[14C] MeAIB uptake by placental villous fragmentsA, Na+-dependent [14C]MeAIB uptake by first trimester (FT) and term placental villous fragments (n= 16 in each group). These data represent system A-mediated transport of [14C]MeAIB and are presented as median and interquartile range. System A activity is significantly higher at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test). B, Na+-dependent [14C]MeAIB uptake by first trimester (n= 6) and term (n= 3) villous fragments in the presence of 5 mm MeAIB, representing SNAT4-mediated activity. SNAT4-mediated activity is significantly lower at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2667314&req=5

fig04: [14C] MeAIB uptake by placental villous fragmentsA, Na+-dependent [14C]MeAIB uptake by first trimester (FT) and term placental villous fragments (n= 16 in each group). These data represent system A-mediated transport of [14C]MeAIB and are presented as median and interquartile range. System A activity is significantly higher at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test). B, Na+-dependent [14C]MeAIB uptake by first trimester (n= 6) and term (n= 3) villous fragments in the presence of 5 mm MeAIB, representing SNAT4-mediated activity. SNAT4-mediated activity is significantly lower at term compared to during first trimester (*P < 0.05, Mann–Whitney U-test).
Mentions: Figure 4A shows that Na+-dependent [14C]MeAIB uptake, representing system A-mediated transport, by term placental villous fragments is significantly higher than uptake by first trimester fragments. This increase could not be attributed to differences in fragment size (Greenwood & Sibley, 2006) as the protein content of first trimester and term placental villous fragments was comparable (mean ±s.e.m.= 501.8 ± 46.3 and 625.7 ± 45.6 μg, respectively, unpaired t test, P= 0.07).

Bottom Line: The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01).In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05).This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.

View Article: PubMed Central - PubMed

Affiliation: Maternal and Fetal Health Research Group, University of Manchester, St Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. michelle.desforges@manchester.ac.uk

ABSTRACT
Placental system A activity is important for the supply of neutral amino acids needed for fetal growth. There are three system A isoforms: SNAT1, SNAT2 and SNAT4, but the contribution of each to system A-mediated transport is unknown. Here, we have used immunohistochemistry to demonstrate that all three isoforms are present in the syncytiotrophoblast suggesting each plays a role in amino acid transport across the placenta. We next tested the hypothesis that the SNAT4 isoform is functional in microvillous plasma membrane vesicles (MVM) from normal human placenta using a method which exploits the unique property of SNAT4 to transport both cationic amino acids as well as the system A-specific substrate MeAIB. The data show that SNAT4 contribution to system A-specific amino acid transport across MVM is higher in first trimester placenta compared to term (approx. 70% and 33%, respectively, P < 0.01). Further experiments performed under more physiological conditions using intact placental villous fragments suggest a contribution of SNAT4 to system A activity in first trimester placenta but minimal contribution at term. In agreement, Western blotting revealed that SNAT4 protein expression is higher in first trimester MVM compared to term (P < 0.05). This study provides the first evidence of SNAT4 activity in human placenta and demonstrates the contribution of SNAT4 to system A-mediated transport decreases between first trimester and term: our data lead us to speculate that at later stages of gestation SNAT1 and/or SNAT2 are more important for the supply of amino acids required for normal fetal growth.

Show MeSH
Related in: MedlinePlus