The Roles of p38 MAPK and ERK1/2 in Coplanar Polychlorinated Biphenyls-Induced Apoptosis of Human Extravillous Cytotrophoblast-Derived Transformed Cells.
OBJECTIVE
The purpose of this study was to investigate the relationships among exposure to coplanar polychlorinated biphenyls (Co-PCBs), the expression of gC1qR and the underlying intracellular apoptotic signaling pathways of human extravillous cytotrophoblast (EVCT)-derived transformed cells (HTR-8/SVneo and HPT-8).


METHODS
Apoptosis in HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis. gClqR expression was examined in the HTR-8/SVneo and HPT-8 cells using real-time qPCR and western blot analyses. The phosphorylations of p38 mitogen-activated protein kinase (p38 MAPK) (Thr180/Tyr182) and extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Thr204) were detected using western blot analyses.


RESULTS
The HTR-8/SVneo and HPT-8 cells treated with Co-PCBs exhibited significantly increased gClqR expression, p38 MAPK/ERK activation and an up-regulation of cellular apoptosis. These effects were abrogated by the application of gC1qR small interfering RNA (siRNA). Furthermore, apoptosis in HTR-8/SVneo and HPT-8 cells was observed upon treatment with Co-PCBs, and these effects were reversed by the p38 MAPK pathway inhibitor SB203580 or the ERK1/2 pathway inhibitor PD098059.


CONCLUSIONS
These data support a mechanism wherein gC1qR plays a crucial p38 MAPK/ERK signaling pathway-dependent role in Co-PCBs-induced apoptosis of human EVCT-derived transformed cells.
Clinical Laboratory, Huangdao District of Traditional Chinese Medicine, Qingdao, China.
Zhu
Z
Liu
Hong-Jie
HJ
Ruan
Ping-Qing
PQ
Gu
Wen-Yan
WY
Ding
Xiao-Hui
XH
Luo
Rong
R
Huang
Wei
W
Zhao
Ling-Juan
LJ
Gao
D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C087299:C1QBP protein, human; D002352:Carrier Proteins; D005419:Flavonoids; D007093:Imidazoles; D024101:Mitochondrial Proteins; D011725:Pyridines; D011078:Polychlorinated Biphenyls; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one