Effects of cadmium on MAPK signalling pathways and HSP70 expression in a human trophoblast cell line

The aim of this work was to provide a greater insight into the possible effects of Cd on signal transduction and stress-related pathways ill reproductive tissues. Cd is a Known placental toxin in both animals and humans. Our experiments were designed to Study the influence of Cd oil MAPK (ERK 1/2, JNK 1/2 and p38MAPK) activation in the extravillous trophoblast cell line, HTR-8/SVneo. used as an experimental model. We also Studied the HSP70 response in cells exposed to Cd, since these proteins may have an important role in conferring protection and tolerance against teratogenic concentrations of the metal. The effects of Cd were compared with those of a well-known toxic agent, H2O2. The metal triggered MAPK activation in a dose- and time-dependent manner. At 30 mu M Cd, Stimulations of about 300%. 550% and 250% were observed for ERK1/2. JNK1/2. and p3SMAPK, respectively. Phosphorylation of ERK1/2 and JNK1/2 was significantly induced after a 1-h exposure to 30 mu M Cd. while that of p38MAPK Occurred only after 8 h. Similarly, H2O2 caused dose- and time-dependent activation of MAPK pathways. Cd potently stimulated HSP70 expression and that of related genes HSP70 A, B and C. H2O2 did not increase HSP70 and HSP70 A and B expression, while temporarily increasing HSP70C transcript levels. In conclusion, Cd triggers different stress responses ill trophoblast cells involving HSP70 and SAPK, and also enhances ERK1/2 phosphorylation. Since MAPK dependent pathways play a crucial role during pregnancy, nonphysiological activation by Cd exposure may disrupt normal Functions in trophoblast cells. (C) 2008 Elsevier Ltd. All rights reserved.