title: Reduced placental taurine transporter (TauT) activity in pregnancies complicated by pre-eclampsia and maternal obesity.
abstract: Taurine is an important nutrient in intrauterine life, being required for fetal organ development and cellular renewal of syncytiotrophoblast (STB), the nutrient transport epithelium of the placenta. As taurine is conditionally essential in human pregnancy, the fetal and placental demand for taurine is met by uptake from maternal blood into STB through the activity of TauT. Pre-eclampsia (PE) and maternal obesity are serious complications of pregnancy, associated with fetal growth restriction (FGR) and abnormal renewal of STB, and maternal obesity is a major risk factor for PE. Here we test the hypothesis that STB TauT activity is reduced in maternal obesity and PE compared to normal pregnancy.STB TauT activity, measured in fragments of placental tissue, was negatively related to maternal BMI over the range 18-46 kg/m(2) in both the first trimester (7-12 weeks gestation) and at term (p < 0.01; linear regression). Neither TauT activity nor expression in the first trimester differed to normal pregnancy at term. STB TauT activity was significantly lower in PE than normal pregnancy (p < 0.01). Neuropeptide Y (NPY), a protein kinase C (PKC) activator which is elevated in PE and obesity, reduced STB TauT activity by 20% (50 pM-50 nM: 2 h) (p < 0.03). Activation of PKC by phorbol 12-myristate-13-acetate (1 μM) reduced TauT activity by 18% (p < 0.05). As TauT activity is inhibited by phosphorylation, we propose that NPY activates PKC in the STB which phosphorylates TauT in PE and maternal obesity.Reduced TauT activity could contribute to dysregulated renewal of STB and FGR that are common to PE and maternal obesity.
authors: Manchester Academic Health Sciences Centre, University of Manchester, Manchester, M13 9WL, UK.
authors: Michelle
authors: M
authors: Desforges
authors: Andrea
authors: A
authors: Ditchfield
authors: Chloe R
authors: CR
authors: Hirst
authors: Claire
authors: C
authors: Pegorie
authors: Kathryn
authors: K
authors: Martyn-Smith
authors: Colin P
authors: CP
authors: Sibley
authors: Susan L
authors: SL
authors: Greenwood
mesh_terms: D015992:Body Mass Index; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D000099247:Taurine Transporters
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009478:Neuropeptide Y; D013755:Tetradecanoylphorbol Acetate; D000099247:Taurine Transporters
references: Am J Physiol Cell Physiol. 2006 Jan;290(1):C305-12
references: 16148032
references: Hypertension. 2005 Dec;46(6):1243-9
references: 16230510
references: Placenta. 2008 Sep;29(9):772-83
references: 18706691
references: Am J Obstet Gynecol. 1989 Nov;161(5):1219-27
references: 2589443
references: Curr Probl Pediatr Adolesc Health Care. 2011 Jul;41(6):158-76
references: 21684471
references: Placenta. 2007 Nov-Dec;28(11-12):1182-91
references: 17675153
references: J Clin Endocrinol Metab. 1989 Aug;69(2):324-8
references: 2753975
references: J Matern Fetal Neonatal Med. 2010 Aug;23(8):880-6
references: 20441409
references: Int J Obes (Lond). 2010 Mar;34(3):420-8
references: 20029373
references: Biochim Biophys Acta. 1995 May 4;1235(2):351-60
references: 7756345
references: Placenta. 1996 Sep;17(7):461-9
references: 8899875
references: Health Trends. 1994;26(1):26-8
references: 10136286
references: Amino Acids. 2004 Jun;26(3):267-71
references: 15221507
references: Obstet Gynecol. 2005 Aug;106(2):250-9
references: 16055572
references: Am J Physiol. 1998 Mar;274(3):E502-9
references: 9530134
references: Am J Pathol. 2003 Feb;162(2):637-43
references: 12547721
references: Placenta. 1995 Apr;16(3):297-308
references: 7638110
references: Am J Obstet Gynecol. 1990 Jan;162(1):253-61
references: 2301500
references: Am J Cardiovasc Dis. 2011;1(1):48-59
references: 22254185
references: Am J Obstet Gynecol. 2006 Jul;195(1):29-39
references: 16579915
references: J Nutr. 1988 Oct;118(10):1169-76
references: 3054019
references: Placenta. 2011 Jan;32(1):1-7
references: 21030077
references: Biol Neonate. 1989;56(4):181-5
references: 2804182
references: Curr Eye Res. 1994 Jul;13(7):523-9
references: 7924416
references: Placenta. 1990 Jan-Feb;11(1):27-33
references: 2158087
references: Pediatr Res. 1972 Jun;6(6):538-47
references: 4625813
references: Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R886-93
references: 15166008
references: N Engl J Med. 1985 Jan 10;312(2):82-90
references: 3880598
references: Amino Acids. 2000;19(3-4):499-507
references: 11140355
references: BJOG. 2010 Jul;117(8):997-1004
references: 20482533
references: Methods Mol Med. 2006;122:253-64
references: 16511986
references: Reproduction. 2003 Jun;125(6):785-90
references: 12773100
references: Ann Med. 1999 Apr;31 Suppl 1:3-6
references: 10342493
references: J Matern Fetal Neonatal Med. 2004 Jun;15(6):356-62
references: 15280104
references: Am J Obstet Gynecol. 2000 Apr;182(4):896-900
references: 10764469
references: FASEB J. 2002 Feb;16(2):231-3
references: 11772953
references: Placenta. 2005 Jan;26(1):93-8
references: 15664417
references: Am J Obstet Gynecol. 1978 Aug 15;131(8):881-7
references: 686088
references: Biochem J. 1991 Jul 1;277 ( Pt 1):53-8
references: 1854347
references: Placenta. 2008 Mar;29(3):274-81
references: 18262644
references: Pediatr Res. 1998 Aug;44(2):233-8
references: 9702920
references: Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1369-79
references: 15284084
references: Acta Physiol (Oxf). 2006 May-Jun;187(1-2):61-73
references: 16734743