PUBLICATION

Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1

Authors
Ma, Y., Zhang, C., Gao, X.B., Luo, H.Y., Chen, Y., Li, H.H., Ma, X., Lu, C.L.
ID
ZDB-PUB-151106-13
Date
2015
Source
Scientific Reports   5: 16093 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Arsenic/adverse effects*
  • Arsenites/adverse effects*
  • Cell Survival/drug effects
  • Down-Regulation/drug effects
  • Embryonic Development/drug effects*
  • Folic Acid/pharmacology*
  • Oxidative Stress/drug effects
  • Reactive Oxygen Species/metabolism
  • Transforming Growth Factor beta/metabolism*
  • Up-Regulation/drug effects
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
26537450 Full text @ Sci. Rep.
CTD
26537450
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping