title: Bisphenol A inhibits proliferation and induces apoptosis in micromass cultures of rat embryonic midbrain cells through the JNK, CREB and p53 signaling pathways.
abstract: Bisphenol A (BPA) has been widely used in the manufacture of polycarbonate plastic, water bottles and food containers. Previous studies have established that BPA could cause developmental toxicity by inhibiting the proliferation and differentiation of rat embryonic midbrain (MB) cells in vitro. However, the underlying mechanisms have not been well studied yet. In the current study, we examined the proliferation and differentiation of MB cells treated with 10(-12)-10(-4)M BPA and found that only 10(-4)M BPA inhibited proliferation and differentiation. Then, we investigated the cell cycle progression and apoptosis of MB cells; 10(-4)M BPA caused an explicit S phase and G2/M phase arrest in the cell cycle and increased the percentage of apoptotic cells. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic-AMP response binding protein (CREB) and the expression of some apoptotic regulatory genes were investigated. BPA (10(-4)M) reduced the phosphorylation of C-Jun N-terminal kinase (JNK) and CREB, and increased the mRNA expression level of Bax and p53. Our findings demonstrated that BPA could cause developmental toxicity through anti-proliferation and pro-apoptosis in MB cells. Multiple signaling pathways, such as the JNK, CREB and p53-mitochondrial apoptosis pathways, participate in these effects.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Lina
authors.initials: L
authors.lastname: Xing
authors.forename: Dan
authors.initials: D
authors.lastname: Kong
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jiang
authors.forename: Lanqin
authors.initials: L
authors.lastname: Shang
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D010636:Phenols / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D017362:Cyclic AMP Response Element-Binding Protein; D048670:MAP Kinase Kinase 4; D010636:Phenols; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C006780:bisphenol A; D000098826:Bisphenol A Compounds