About: Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast     Goto   Sponge   NotDistinct   Permalink

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  • Antenatal glucocorticoid administration is used in cases of fetuses at risk to be born prematurely to enhance fetal pulmonary surfactant production and prevent infant respiratory distress syndrome. The CYP1A1 is the most important xenobiotic-metabolizing cytochrome P450 enzyme in the human placenta. Importantly, CYP1A1 generates reactive species and its placental activity is elevated in smoking women. CYP1A1 expression is mainly controlled by aryl hydrocarbon receptor (AHR) ligands. Glucocorticoid co-regulation of CYP1A1 has been described in various cell types but has not been systematically examined in the human placental trophoblast. We studied the effects of the glucocorticoids dexamethasone and betamethasone on inducibility of CYP1A1 and other AHR target genes CYP1A2, CYP1B1, UGT1A1 (UDP-glucuronosyltransferase 1A1) and BCRP (Breast cancer resistance protein) by prototype AHR ligand 3-methylcholanthrene (3MC) in isolated human placental trophoblast culture. We show that glucocorticoids alone had no effect on activity and protein/mRNA expression of CYP1A1 and little effect on mRNA expression of other AHR target genes. However, glucocorticoids significantly stimulated CYP1A1 mRNA, but not CYP1A2, CYP1B1, UGT1A1 and BCRP mRNAs, induction mediated by the AHR ligand. Consistently, glucocorticoids significantly augmented 7-ethoxyresorufin-O-deethylation (EROD) enzymatic activity in primary human placental trophoblast. Dexamethasone did not influence AHR and ARNT (Aryl hydrocarbon receptor nuclear translocator) mRNAs, suggesting that this phenomenon is not due to AHR or ARNT up-regulation by glucocorticoids in human trophoblast. In conclusion, our data suggest that glucocorticoids have no effect on AHR target genes expression per se, but they may potentiate CYP1A1 induction in human term placental trophoblast.
  • Antenatal glucocorticoid administration is used in cases of fetuses at risk to be born prematurely to enhance fetal pulmonary surfactant production and prevent infant respiratory distress syndrome. The CYP1A1 is the most important xenobiotic-metabolizing cytochrome P450 enzyme in the human placenta. Importantly, CYP1A1 generates reactive species and its placental activity is elevated in smoking women. CYP1A1 expression is mainly controlled by aryl hydrocarbon receptor (AHR) ligands. Glucocorticoid co-regulation of CYP1A1 has been described in various cell types but has not been systematically examined in the human placental trophoblast. We studied the effects of the glucocorticoids dexamethasone and betamethasone on inducibility of CYP1A1 and other AHR target genes CYP1A2, CYP1B1, UGT1A1 (UDP-glucuronosyltransferase 1A1) and BCRP (Breast cancer resistance protein) by prototype AHR ligand 3-methylcholanthrene (3MC) in isolated human placental trophoblast culture. We show that glucocorticoids alone had no effect on activity and protein/mRNA expression of CYP1A1 and little effect on mRNA expression of other AHR target genes. However, glucocorticoids significantly stimulated CYP1A1 mRNA, but not CYP1A2, CYP1B1, UGT1A1 and BCRP mRNAs, induction mediated by the AHR ligand. Consistently, glucocorticoids significantly augmented 7-ethoxyresorufin-O-deethylation (EROD) enzymatic activity in primary human placental trophoblast. Dexamethasone did not influence AHR and ARNT (Aryl hydrocarbon receptor nuclear translocator) mRNAs, suggesting that this phenomenon is not due to AHR or ARNT up-regulation by glucocorticoids in human trophoblast. In conclusion, our data suggest that glucocorticoids have no effect on AHR target genes expression per se, but they may potentiate CYP1A1 induction in human term placental trophoblast. (en)
Title
  • Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast
  • Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast (en)
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  • Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast
  • Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast (en)
skos:notation
  • RIV/00216208:11160/13:10145998!RIV14-GA0-11160___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(ED0030/01/01), P(GAP304/10/0149), P(GAP503/10/0579), P(GBP303/12/G163)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 71948
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11160/13:10145998
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • placenta; glucocorticoids; cytochrome P450; CYP1A1; aryl hydrocarbon receptor; trophoblast (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • CZ - Česká republika
http://linked.open...ontrolniKodProRIV
  • [40A4A776D70F]
http://linked.open...i/riv/nazevZdroje
  • Journal of Applied Biomedicine
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 11
http://linked.open...iv/tvurceVysledku
  • Dvořák, Zdeněk
  • Pávek, Petr
  • Vrzal, Radim
  • Stejskalová, Lucie
  • Rulcová, Alice
http://linked.open...ain/vavai/riv/wos
  • 000315854000005
issn
  • 1214-021X
number of pages
http://bibframe.org/vocab/doi
  • 10.2478/v10136-012-0022-y
http://localhost/t...ganizacniJednotka
  • 11160
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