title: L-methionine placental uptake: characterization and modulation in gestational diabetes mellitus.
abstract: Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of (14)C-l-methionine ((14)C-l-Met). The (14)C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y(+)LAT2 is also present. Comparison of (14)C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b(0+) and a greater contribution of system y(+)LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease (14)C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter (14)C-l-Met placental uptake, although it changes the nature of transporters involved in that process.
authors: 1Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
authors: João R
authors: JR
authors: Araújo
authors: Ana
authors: A
authors: Correia-Branco
authors: Carla
authors: C
authors: Ramalho
authors: Pedro
authors: P
authors: Gonçalves
authors: Maria J
authors: MJ
authors: Pinho
authors: Elisa
authors: E
authors: Keating
authors: Fátima
authors: F
authors: Martel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001692:Biological Transport; D016022:Case-Control Studies; D002460:Cell Line; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D027283:Large Neutral Amino Acid-Transporter 1 / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; C419196:LAT2 protein, human; D027283:Large Neutral Amino Acid-Transporter 1; D020738:Leptin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008715:Methionine; D058539:Phosphatidylinositol 3-Kinase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords:  l-methionine; gestational diabetes; placenta; transport
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