PMID- 30402708
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20211209
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 7
DP  - 2019 Jul
TI  - Prenatal Exposure to Benzophenone-3 Impairs Autophagy, Disrupts RXRs/PPARgamma 
      Signaling, and Alters Epigenetic and Post-Translational Statuses in Brain 
      Neurons.
PG  - 4820-4837
LID - 10.1007/s12035-018-1401-5 [doi]
AB  - The UV absorber benzophenone-3 (BP-3) is the most extensively used chemical 
      substance in various personal care products. Despite that BP-3 exposure is 
      widespread, knowledge about the impact of BP-3 on the brain development is 
      negligible. The present study aimed to explore the mechanisms of prenatal 
      exposure to BP-3 in neuronal cells, with particular emphasis on autophagy and 
      nuclear receptors signaling as well as the epigenetic and post-translational 
      modifications occurring in response to BP-3. To observe the impact of prenatal 
      exposure to BP-3, we administered BP-3 to pregnant mice, and next, we isolated 
      brain tissue from pretreated embryos for primary cell neocortical culture. Our 
      study revealed that prenatal exposure to BP-3 (used in environmentally relevant 
      doses) impairs autophagy in terms of BECLIN-1, MAP1LC3B, autophagosomes, and 
      autophagy-related factors; disrupts the levels of retinoid X receptors (RXRs) and 
      peroxisome proliferator-activated receptor gamma (PPARgamma); alters epigenetic 
      status (i.e., attenuates HDAC and sirtuin activities); inhibits 
      post-translational modifications in terms of global sumoylation; and dysregulates 
      expression of neurogenesis- and neurotransmitter-related genes as well as miRNAs 
      involved in pathologies of the nervous system. Our study also showed that BP-3 
      has good permeability through the BBB. We strongly suggest that BP-3-evoked 
      effects may substantiate a fetal basis of the adult onset of neurological 
      diseases, particularly schizophrenia and Alzheimer's disease.
FAU - Wnuk, Agnieszka
AU  - Wnuk A
AD  - Institute of Pharmacology, Department of Experimental Neuroendocrinology, 
      Laboratory of Molecular Neuroendocrinology, Polish Academy of Sciences, Smetna 
      Street 12, 31-343, Krakow, Poland.
FAU - Rzemieniec, Joanna
AU  - Rzemieniec J
AD  - Institute of Pharmacology, Department of Experimental Neuroendocrinology, 
      Laboratory of Molecular Neuroendocrinology, Polish Academy of Sciences, Smetna 
      Street 12, 31-343, Krakow, Poland.
FAU - Staron, Jakub
AU  - Staron J
AD  - Institute of Pharmacology, Department of Medicinal Chemistry, Polish Academy of 
      Sciences, Smetna Street 12, 31-343, Krakow, Poland.
FAU - Litwa, Ewa
AU  - Litwa E
AD  - Institute of Pharmacology, Department of Experimental Neuroendocrinology, Polish 
      Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.
FAU - Lason, Wladyslaw
AU  - Lason W
AD  - Institute of Pharmacology, Department of Experimental Neuroendocrinology, Polish 
      Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.
FAU - Bojarski, Andrzej
AU  - Bojarski A
AD  - Institute of Pharmacology, Department of Medicinal Chemistry, Polish Academy of 
      Sciences, Smetna Street 12, 31-343, Krakow, Poland.
FAU - Kajta, Malgorzata
AU  - Kajta M
AUID- ORCID: 0000-0003-0616-7031
AD  - Institute of Pharmacology, Department of Experimental Neuroendocrinology, 
      Laboratory of Molecular Neuroendocrinology, Polish Academy of Sciences, Smetna 
      Street 12, 31-343, Krakow, Poland. kajta@if-pan.krakow.pl.
LA  - eng
GR  - 2014/13/N/NZ4/04845/National Science Centre of Poland/
PT  - Journal Article
DEP - 20181106
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Benzophenones)
RN  - 0 (MicroRNAs)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinoid X Receptors)
RN  - 95OOS7VE0Y (oxybenzone)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 3.5.1.- (Sirtuins)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Autophagosomes/drug effects/metabolism
MH  - Autophagy/*drug effects/genetics
MH  - Benzophenones/administration & dosage/*toxicity
MH  - Blood-Brain Barrier/drug effects/pathology
MH  - Brain/*pathology
MH  - Embryo, Mammalian/cytology
MH  - *Epigenesis, Genetic/drug effects
MH  - Female
MH  - Histone Acetyltransferases/metabolism
MH  - Histone Deacetylases/metabolism
MH  - Mice
MH  - MicroRNAs/genetics/metabolism
MH  - Neurogenesis/drug effects/genetics
MH  - Neurons/drug effects/metabolism/*pathology
MH  - Neurotransmitter Agents/metabolism
MH  - PPAR gamma/*metabolism
MH  - Permeability
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*genetics/*pathology
MH  - Protein Processing, Post-Translational/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Retinoid X Receptors/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuins/metabolism
MH  - Sumoylation
PMC - PMC6647400
OTO - NOTNLM
OT  - Autophagy
OT  - BP-3
OT  - Benzophenone-3
OT  - Neuronal cell
OT  - Prenatal exposure
OT  - miRNA
COIS- The authors declare that they have no competing interests.
EDAT- 2018/11/08 06:00
MHDA- 2019/12/21 06:00
PMCR- 2018/11/06
CRDT- 2018/11/08 06:00
PHST- 2018/09/06 00:00 [received]
PHST- 2018/10/17 00:00 [accepted]
PHST- 2018/11/08 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2018/11/08 06:00 [entrez]
PHST- 2018/11/06 00:00 [pmc-release]
AID - 10.1007/s12035-018-1401-5 [pii]
AID - 1401 [pii]
AID - 10.1007/s12035-018-1401-5 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Jul;56(7):4820-4837. doi: 10.1007/s12035-018-1401-5. Epub 
      2018 Nov 6.