Low-level bisphenol A increases production of glial fibrillary acidic protein in differentiating astrocyte progenitor cells through excessive STAT3 and Smad1 activation.
The effects of bisphenol A (BPA) on the differentiation of serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, were examined. SFME cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10ng/ml bone morphogenetic protein 2 (BMP2) to increase glial fibrillary acidic protein (GFAP) expression and induce cell differentiation. Various concentrations of BPA (0.1 pg/ml-1 microg/ml) were then added to determine their effects on the cell differentiation. SFME cells were effectively differentiated by LIF and BMP2 in completely serum-free cultures. Cell proliferation following cell differentiation was not significantly affected by low-level BPA. However, GFAP expression was significantly increased in SFME cells in the presence of 1-100 pg/ml BPA. These increases were due to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA.
Yamaguchi
Hideaki
H
Graduate School of Environmental Sciences, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan. yamaguch@aomori-u.ac.jp
Zhu
Jun
J
Yu
Tao
T
Sasaki
Kazuo
K
Umetsu
Hironori
H
Kidachi
Yumi
Y
Ryoyama
Kazuo
K
D000395:Air Pollutants, Occupational / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001559:Benzhydryl Compounds; D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016895:Culture Media, Serum-Free; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D010636:Phenols / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051898:Smad1 Protein / Q000378:metabolism*; D051905:Smad6 Protein / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D051792:Basic Helix-Loop-Helix Proteins; D001559:Benzhydryl Compounds; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D010636:Phenols; D050796:STAT3 Transcription Factor; D051898:Smad1 Protein; D051905:Smad6 Protein; D016212:Transforming Growth Factor beta; C525719:Bmp2 protein, mouse; C507837:LIF protein, human; C507838:Lif protein, mouse; C512773:Olig2 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds