title: Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1.
abstract: As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels.
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Gao
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Luo
authors.affiliation: MOE Key Laboratory of Bioinformatics, TNLIST Bioinformatics Division &Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Dalian Medical University, Dalian, China.|Department of Cardiology, Institute of Cardiovascular Disease, First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Hui-hua
authors.initials: HH
authors.lastname: Li
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China.|Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Cai-Ling
authors.initials: CL
authors.lastname: Lu
mesh_terms: D000818:Animals; D001151:Arsenic / Q000009:adverse effects*; D018053:Arsenites / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005492:Folic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018053:Arsenites; C079678:Gdf3 protein, zebrafish; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D005492:Folic Acid; C015001:arsenite; D001151:Arsenic