PMID- 33212164
OWN - NLM
STAT- MEDLINE
DCOM- 20211020
LR  - 20211020
IS  - 1872-9738 (Electronic)
IS  - 0892-0362 (Linking)
VI  - 83
DP  - 2021 Jan-Feb
TI  - Characterizing the effects of in utero valproic acid exposure on NF-kappaB signaling 
      in CD-1 mouse embryos during neural tube closure.
PG  - 106941
LID - S0892-0362(20)30191-4 [pii]
LID - 10.1016/j.ntt.2020.106941 [doi]
AB  - Nuclear factor kappa B (NF-kappaB) is a heterodimer of protein subunits p65 and p50, 
      that regulates the expression of a large number of genes related to cell growth 
      and proliferation. The p65 subunit is activated after phosphorylation by Pim-1, 
      while the p50 subunit is the cleaved product of its precursor molecule p105. 
      Valproic acid (VPA), an antiepileptic drug, is a known teratogen and its exposure 
      during pregnancy is associated with 1-2% of neural tube defects in the offspring. 
      The current study aimed at investigating the effects of in utero VPA exposure on 
      the key components of the NF-kappaB signaling pathway including p65, p50, and Pim-1 
      in CD-1 mouse embryos during the critical period of neural tube closure. Here we 
      report that p65, Pim-1 and p105/p50 mRNA were significantly (p < 0.05) 
      downregulated at 1 and 3 h following in utero exposure to a teratogenic dose 
      (400 mg/kg) of VPA in gestational day (GD)9 exposed embryos. At GD13 heads of 
      control, non-exencephalic and exencephalic embryos were used for analysis and we 
      found significant upregulation of p65 protein expression in non-exencephalic GD13 
      heads while p50 protein levels were significantly downregulated in both 
      non-exencephalic and exencephalic groups. On the other hand, p65 and p50 protein 
      levels remained unchanged in the nuclear extracts of the VPA-exposed 
      non-exencephalic and exencephalic GD13 embryo heads. The reported results suggest 
      that VPA exposure perturbates p65, p105/p50, Pim-1 transcript and p65/p50 protein 
      levels in mouse embryos.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Shafique, Sidra
AU  - Shafique S
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Winn, Louise M
AU  - Winn LM
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada; School of Environmental Studies, Queen's University, 
      Kingston, Ontario K7L 3N6, Canada. Electronic address: winnl@queensu.ca.
LA  - eng
GR  - MOP 115188/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201116
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Anticonvulsants)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Neurotoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 147257-52-1 (Nfkb1 protein, mouse)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.11.1 (Pim1 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/administration & dosage/toxicity
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Male
MH  - Maternal-Fetal Exchange
MH  - Mice
MH  - NF-kappa B/genetics/*metabolism
MH  - NF-kappa B p50 Subunit/genetics/metabolism
MH  - Neural Tube/*drug effects/*embryology/metabolism
MH  - Neural Tube Defects/chemically induced/embryology/metabolism
MH  - Neurotoxins/administration & dosage/toxicity
MH  - Neurulation/drug effects/physiology
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-pim-1/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Transcription Factor RelA/genetics/metabolism
MH  - Valproic Acid/administration & dosage/*toxicity
OTO - NOTNLM
OT  - Mouse embryo
OT  - NF-kappaB
OT  - Neural tube defects
OT  - Valproic acid
OT  - p105
OT  - p50
OT  - p65
EDAT- 2020/11/20 06:00
MHDA- 2021/10/21 06:00
CRDT- 2020/11/19 20:09
PHST- 2020/08/11 00:00 [received]
PHST- 2020/11/09 00:00 [revised]
PHST- 2020/11/11 00:00 [accepted]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2021/10/21 06:00 [medline]
PHST- 2020/11/19 20:09 [entrez]
AID - S0892-0362(20)30191-4 [pii]
AID - 10.1016/j.ntt.2020.106941 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2021 Jan-Feb;83:106941. doi: 10.1016/j.ntt.2020.106941. 
      Epub 2020 Nov 16.