The proteomic and genomic teratogenicity elicited by valproic acid is preventable with resveratrol and α-tocopherol

Yeh Chen, Ping Xiao Lin, Chiu Lan Hsieh, Chiung Chi Peng, Robert Y. Peng

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7 Citations (Scopus)

Abstract

Conclusions: VPA alters the expression of PEBP1, BHMT, MYL1, ALB and FLNC that are closely related with metabolic myopathies, myogenesis, albumin gene expression, and haemolytic anemia. On the other hand, VPA directly inhibits the betaine-dependent remethylation pathway. Taken together, VPA elicits hemorrhagic myoliposis via these action mechanisms, and RV and vit E are effective for alleviation of such adverse effects.

Methodology/Principal Findings: VPA (60 mM) was applied to 36 chicken embryos at HH stage 10 (day-1.5). Resveratrol (RV) and vitamin E (vit E) (each at 0.2 and 2.0 mM) were applied simultaneously to explore the alleviation effect. The proteins in the cervical muscles of the day-1 chicks were analyzed using 2Delectrophoresis and LC/MS/MS. While the genomics associated with each specific protein alteration was examined with RT-PCR and qPCR. At earlier embryonic stage, VPA downregulated PEBP1 and BHMT genes and at the same time upregulated MYL1, ALB and FLNC genes significantly (p<0.05) without affecting PKM2 gene. Alternatively, VPA directly inhibited the folate-independent (or the betaine-dependent) remethylation pathway. These features were effectively alleviated by RV and vit E.

Background: Previously, we reported that valproic acid (VPA), a common antiepileptic drug and a potent teratogenic, dowregulates RBP4 in chicken embryo model (CEM) when induced by VPA. Whether such teratogenicity is associated with more advanced proteomic and genomic alterations, we further performed this present study.

Original languageEnglish
Article number0116534
JournalPLoS ONE
Volume9
Issue number12
DOIs
Publication statusPublished - 2014 Dec 31

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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