title: Exposure to ethanol and nicotine induces stress responses in human placental BeWo cells.
abstract: Human placental trophoblastic cancer BeWo cells can be used as a model of placental trophoblasts. We found that combined exposure to relevant exposure concentrations of ethanol (2‰) and nicotine (15 μM) induces an increase in the amount of reactive oxygen species (ROS). Neither ethanol or nicotine alone, nor their combination affected cell viability. However, nicotine decreased cell proliferation, both alone and combined with ethanol. Nicotine increased the expression of the endoplasmic reticulum (ER)-stress related protein GRP78/BiP, but not another marker of ER-stress, IRE1α. We also studied the effects of nicotine and/or ethanol on phosphorylation and expression of three mitogen-activated protein kinases (MAPKs), i.e. JNK, p38 and ERK1/2. Nicotine decreased the phosphorylation of JNK and also had similar effect on total amount of this protein. Phosphorylation and expression of p38 were increased 1.7- and 1.6-fold, respectively, by nicotine alone, and 1.9- and 2.1-fold by the combined treatment. Some increase (1.8-fold) was also seen in the phosphorylation of ERK2 at 48 h, in cells exposed to both ethanol and nicotine. This study shows that ethanol and nicotine, which harm the development of fetus may induce both oxidative and ER stress responses in human placental trophoblastic cells, implicating these mechanisms in their fetotoxic effects.
authors.affiliation: Faculty of Health Sciences, School of Pharmacy/Toxicology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Jenni K
authors.initials: JK
authors.lastname: Repo
authors.forename: Maija
authors.initials: M
authors.lastname: Pesonen
authors.forename: Chiara
authors.initials: C
authors.lastname: Mannelli
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vähäkangas
authors.forename: Jarkko
authors.initials: J
authors.lastname: Loikkanen
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D009538:Nicotine / Q000633:toxicity*; D010766:Phosphorylation; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D000431:Ethanol; D009538:Nicotine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ER-stress; GRP78/BiP; Human trophoblastic cells; MAPKs; Placental toxicity; ROS