Hepatocyte growth factor induced human trophoblast motility involves phosphatidylinositol-3-kinase, mitogen-activated protein kinase, and inducible nitric oxide synthase

被引:79
作者
Cartwright, JE [1 ]
Tse, WK [1 ]
Whitley, GS [1 ]
机构
[1] St George Hosp, Sch Med, Dept Biochem & Immunol, London SW17 ORE, England
基金
英国惠康基金;
关键词
trophoblast; hepatocyte growth factor; nitric oxide; motility; pregnancy; phosphatidylinositol-3-kinase; mitogen-activated protein kinase; nitric oxide synthase;
D O I
10.1006/excr.2002.5616
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hepatocyte growth factor (HGF) increases human trophoblast motility and invasion, an effect which is abrogated when inducible nitric oxide synthase (iNOS) is inhibited. In this study we have investigated the pathways involved in the regulation of trophoblast motility. Both basal and HGF-stimulated motility of the extravillous trophoblast cell line, SGHPL-4, were inhibited in a dose-dependent manner by the phosphatidylinositol-3-kinase (PI3-kinase) inhibitor, LY294002. HGF-stimulated iNOS expression was also inhibited by LY294002 and direct activation of PI3-kinase, using the peptide 740Y-P, led to an increase in iNOS expression and cell motility. Pretreatment with rapamycin, which acts at a point distal to P13-kinase activation, also inhibited basal and HGF-stimulated motility. Inhibition of the p42/p44 mitogen activated protein kinase (MAPK) pathway but not the p38 MAPK pathway had significant inhibitory effects on HGF-stimulated but not basal trophoblast motility. Inhibition of p42/p44 MAPK also inhibited HGF-induced iNOS expression. This data demonstrate that the PI3kinase signaling pathway is involved in basal trophoblast motility and that both MAPK and P13-kinase signaling pathways are important in HGF-stimulated motility and iNOS expression. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:219 / 226
页数:8
相关论文
共 46 条
[1]   Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells - Evaluation of the role of the nitric oxide signaling pathway and potential defects in hypertension [J].
Begum, N ;
Ragolia, L ;
Rienzie, J ;
McCarthy, M ;
Duddy, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (39) :25164-25170
[2]   ESSENTIAL ROLE FOR THE C-MET RECEPTOR IN THE MIGRATION OF MYOGENIC PRECURSOR CELLS INTO THE LIMB BUD [J].
BLADT, F ;
RIETHMACHER, D ;
ISENMANN, S ;
AGUZZI, A ;
BIRCHMEIER, C .
NATURE, 1995, 376 (6543) :768-771
[3]   Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide [J].
Cartwright, JE ;
Holden, DP ;
Whitley, GS .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 128 (01) :181-189
[4]  
Chen YQ, 1998, J IMMUNOL, V161, P4950
[5]  
Choy M Y, 2000, Early Pregnancy, V4, P124
[6]   The phagocytic activity of human first trimester extravillous trophoblast [J].
Choy, MY ;
Manyonda, IT .
HUMAN REPRODUCTION, 1998, 13 (10) :2941-2949
[7]   Trophoblast pseudo-vasculogenesis: faking it with endothelial adhesion receptors [J].
Damsky, CH ;
Fisher, SJ .
CURRENT OPINION IN CELL BIOLOGY, 1998, 10 (05) :660-666
[8]   Stimulation of mitogenesis by a cell-permeable PI 3-kinase binding peptide [J].
Derossi, D ;
Williams, EJ ;
Green, PJ ;
Dunican, DJ ;
Doherty, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 251 (01) :148-152
[9]  
Díaz-Guerra MJM, 1999, J IMMUNOL, V162, P6184
[10]   New insights into the control of MAP kinase pathways [J].
English, J ;
Pearson, G ;
Wilsbacher, J ;
Swantek, J ;
Karandikar, M ;
Xu, SC ;
Cobb, MH .
EXPERIMENTAL CELL RESEARCH, 1999, 253 (01) :255-270