Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions

被引:110
作者
Knerr, I
Schubert, SW
Wich, C
Amann, K
Aigner, T
Vogler, T
Jung, R
Dötsch, J
Rascher, W
Hashemolhosseini, S [1 ]
机构
[1] Univ Erlangen Nurnberg, Inst Biochem, D-8520 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Hosp Children & Adolescents, D-8520 Erlangen, Germany
[3] Univ Erlangen Nurnberg, Dept Pathol, D-8520 Erlangen, Germany
关键词
Connexin-43; glial cells missing a; hypoxia; syncytin; syncytiotrophoblast;
D O I
10.1016/j.febslet.2005.06.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glial cells missing a (GCMa) belongs to a new transcription factor family. Syncytin was shown to be a target gene of GCMa. Here, we demonstrate that the protein kinase A (PKA) pathway acts upstream of GCMa. After transient transfection of BeWo cells with PKA, GCMa transcriptional activity and both GCMa and syncytin transcripts were upregulated. This increase was accompanied by further cellular differentiation. Using normoxic or hypoxic conditions to mimic pathophysiological settings known to diminish trophoblast differentiation, we found that gene repressive effects of oxygen deficiency were compensated by the induction of the PKA pathway. We propose that GCMa-driven syncytin expression is the key mechanism for syncytiotrophoblast formation. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:3991 / 3998
页数:8
相关论文
共 36 条
[1]   The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta [J].
Anson-Cartwright, L ;
Dawson, K ;
Holmyard, D ;
Fisher, SJ ;
Lazzarini, RA ;
Cross, JC .
NATURE GENETICS, 2000, 25 (03) :311-314
[2]   An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor [J].
Blond, JL ;
Lavillette, D ;
Cheynet, V ;
Bouton, O ;
Oriol, G ;
Chapel-Fernandes, S ;
Mandrand, B ;
Mallet, F ;
Cosset, FL .
JOURNAL OF VIROLOGY, 2000, 74 (07) :3321-3329
[3]   Decreased placental GCM1 (glial cells missing) gene expression in pre-eclampsia [J].
Chen, CP ;
Chen, CY ;
Yang, YC ;
Su, TH ;
Chen, H .
PLACENTA, 2004, 25 (05) :413-421
[4]   Isolation and characterization of the human syncytin gene promoter [J].
Cheng, YH ;
Richardson, BD ;
Hubert, MA ;
Handwerger, S .
BIOLOGY OF REPRODUCTION, 2004, 70 (03) :694-701
[5]   Structure of the GCM domain-DNA complex:: a DNA-binding domain with a novel fold and mode of target site recognition [J].
Cohen, SX ;
Moulin, M ;
Hashemolhosseini, S ;
Kilian, K ;
Wegner, M ;
Müller, CW .
EMBO JOURNAL, 2003, 22 (08) :1835-1845
[6]   Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae [J].
Dupressoir, A ;
Marceau, G ;
Vernochet, C ;
Bénit, L ;
Kanellopoulos, C ;
Sapin, V ;
Heidmann, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (03) :725-730
[7]   Direct involvement of HERV-W env glycoprotein in human trophoblast cell fusion and differentiation [J].
Frendo, JL ;
Olivier, D ;
Cheynet, V ;
Blond, JL ;
Bouton, O ;
Vidaud, M ;
Rabreau, M ;
Evain-Brion, D ;
Mallet, F .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (10) :3566-3574
[8]   Involvement of connexin 43 in human trophoblast cell fusion and differentiation [J].
Frendo, JL ;
Cronier, L ;
Bertin, G ;
Guibourdenche, J ;
Vidaud, M ;
Evain-Brion, D ;
Malassiné, A .
JOURNAL OF CELL SCIENCE, 2003, 116 (16) :3413-3421
[9]   Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy [J].
Gifford, RW ;
August, PA ;
Cunningham, G ;
Green, LA ;
Lindheimer, MD ;
McNellis, D ;
Roberts, JM ;
Sibai, BM ;
Taler, SJ .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2000, 183 (01) :S1-S22
[10]   IN-SITU REGULATION OF CELL-CELL COMMUNICATION BY THE CAMP-DEPENDENT PROTEIN-KINASE AND PROTEIN-KINASE-C [J].
GODWIN, AJ ;
GREEN, LM ;
WALSH, MP ;
MCDONALD, JR ;
WALSH, DA ;
FLETCHER, WH .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1993, 128 :293-307