TY - JOUR
T1 - Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis
AU - McAleer, M. F.
AU - Tuan, R. S.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Proper functioning of trophoblastic cells is essential for maintenance of the placenta and development of the embryo/fetus. Exposure of trophoblasts to toxic exogenous factors, such as cadmium (Cd), perturbs placental function and affects fetal outcome. Cellular responses to Cd exposure include induction of the metal-binding protein, metallothionein (MT), and initiation of apoptosis. To analyze the functional relationship between cellular MT levels and apoptosis in trophoblasts, we have examined the effects of DNA transfection-mediated alterations in MT levels on trophoblastic function and apoptosis, with and without Cd exposure, using the trophoblast-like JEG-3 human choriocarcinoma cell line. JEG-3 cells stably transfected with human MT-IIa cDNA expression constructs, in either sense or antisense orientation, were unchanged in human chorionic gonadotropin (hCG) production or expression of the apoptotic markers, bcl-2 and CPP-32. However, MT overexpression significantly prolonged the recovery time of intracellular Ca flux, whereas reduced basal MT increased the incidence of apoptosis as determined by morphology and terminal deoxynucleotidyl end labeling (TUNEL) staining. Upon Cd exposure, a dose-dependent decrease in hCG secretion was seen in all JEG-3 cultures, without any correlation to basal MT expression. Basal MT levels, however, significantly affected the extent of apoptosis, the incidence being inversely related to basal MT level. These results suggest that while MT does not ameliorate heavy-metal induced perturbation of some trophoblastic functions, its expression is critical for protection of these cells from Cd-induced apoptosis and could act to maintain placental integrity in cases of maternal Cd exposure.
AB - Proper functioning of trophoblastic cells is essential for maintenance of the placenta and development of the embryo/fetus. Exposure of trophoblasts to toxic exogenous factors, such as cadmium (Cd), perturbs placental function and affects fetal outcome. Cellular responses to Cd exposure include induction of the metal-binding protein, metallothionein (MT), and initiation of apoptosis. To analyze the functional relationship between cellular MT levels and apoptosis in trophoblasts, we have examined the effects of DNA transfection-mediated alterations in MT levels on trophoblastic function and apoptosis, with and without Cd exposure, using the trophoblast-like JEG-3 human choriocarcinoma cell line. JEG-3 cells stably transfected with human MT-IIa cDNA expression constructs, in either sense or antisense orientation, were unchanged in human chorionic gonadotropin (hCG) production or expression of the apoptotic markers, bcl-2 and CPP-32. However, MT overexpression significantly prolonged the recovery time of intracellular Ca flux, whereas reduced basal MT increased the incidence of apoptosis as determined by morphology and terminal deoxynucleotidyl end labeling (TUNEL) staining. Upon Cd exposure, a dose-dependent decrease in hCG secretion was seen in all JEG-3 cultures, without any correlation to basal MT expression. Basal MT levels, however, significantly affected the extent of apoptosis, the incidence being inversely related to basal MT level. These results suggest that while MT does not ameliorate heavy-metal induced perturbation of some trophoblastic functions, its expression is critical for protection of these cells from Cd-induced apoptosis and could act to maintain placental integrity in cases of maternal Cd exposure.
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U2 - 10.1089/109793301316882522
DO - 10.1089/109793301316882522
M3 - Article
C2 - 11689154
AN - SCOPUS:0034941959
SN - 1097-9336
VL - 14
SP - 25
EP - 42
JO - In Vitro and Molecular Toxicology: Journal of Basic and Applied Research
JF - In Vitro and Molecular Toxicology: Journal of Basic and Applied Research
IS - 1
ER -