PMID- 28970181
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20180625
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 63
DP  - 2017 Dec
TI  - Altered expression of genes involved in programmed cell death in primary cultured 
      rat cerebellar granule cells acutely challenged with tetrabromobisphenol A.
PG  - 126-136
LID - S0161-813X(17)30203-6 [pii]
LID - 10.1016/j.neuro.2017.09.014 [doi]
AB  - In the present study, primary cultures of rat cerebellar granule cells (CGC) and 
      the RT(2) Profiler PCR array were used to examine the effect of acutely applied 
      brominated flame retardant tetrabromobisphenol A (TBBPA) on the expression of 84 
      genes related to the main modes of programmed cell death. CGC, at the 7th day of 
      culture, were exposed to 10 or 25muM TBBPA for 30min. Then, 3, 6, and 24h later, 
      the viability of the cells was examined by the staining with propidium iodide 
      (PI) or using the calcein/ethidium homodimer (CA/ET) live/dead kit, and RNA was 
      extracted for the evaluation of gene expression by RT-PCR. At 3, 6 and 24h after 
      the treatment, the number of viable neurons decreased, according to the PI 
      staining method, to 75%, 58% and 41%, respectively, and with the CA/ET method to 
      65%, 58% and 28%, respectively. In CGC analyzed 3h after the treatment with 25muM 
      TBBPA or 6h after 10muM TBBPA, the only change in the gene expression was a 
      reduction in the expression of Tnf, which is associated with autophagy and may 
      activate some pro-apoptotic proteins. Six hours after 25muM TBBPA, only 2 genes 
      were over-expressed, a pro-apoptotic Tnfrsf10b and Irgm, which is related to 
      autophagy, and the genes that were suppressed included the anti-apoptotic gene 
      Xiap, the necrosis-related Commd4, pro-apoptotic Abl1, 5 genes involved in 
      autophagy (App, Atg3, Mapk8, Pten, and Snca) and 2 genes that participate in two 
      metabolic pathways: Atp6v1g2 (pro-apoptotic and necrosis) and Tnf (pro-apoptotic, 
      autophagy). Autophagy-related Snca and Tnf remained under-expressed 24h after 
      treatment with 25muM TBBPA, which was accompanied by the over-expression of the 
      pro-apoptotic Casp6, the anti-apoptotic Birc3, 2 genes related to autophagy (Htt 
      and Irgm) and 2 genes (Fas and Tp53) that are involved in both apoptosis 
      (pro-apoptotic) and autophagy. These results show a complex pattern of 
      TBBPA-evoked changes in the expression of the genes involved in the programmed 
      neuronal death, indicating no induction of programmed necrosis, an early 
      suppression of the autophagy and anti-apoptotic genes, followed by a delayed 
      activation of genes associated with apoptosis.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Lenart, Jacek
AU  - Lenart J
AD  - Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy 
      of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland. Electronic address: 
      jlenart@imdik.pan.pl.
FAU - Zieminska, Elzbieta
AU  - Zieminska E
AD  - Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy 
      of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
FAU - Diamandakis, Dominik
AU  - Diamandakis D
AD  - Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy 
      of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
FAU - Lazarewicz, Jerzy W
AU  - Lazarewicz JW
AD  - Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy 
      of Sciences, Pawinskiego 5, 02-106, Warsaw, Poland.
LA  - eng
PT  - Journal Article
DEP - 20170929
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (Polybrominated Biphenyls)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factors)
RN  - 0 (bcl-2-Associated X Protein)
RN  - FQI02RFC3A (tetrabromobisphenol A)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects
MH  - Autophagy
MH  - Autophagy-Related Proteins/genetics/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebellum/*cytology
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/*drug effects
MH  - Neurons/*drug effects/metabolism
MH  - Polybrominated Biphenyls/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Time Factors
MH  - Tumor Necrosis Factors/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Brominated flame retardants
OT  - Necrosis
OT  - Neurotoxicity
OT  - Primary neuronal cultures
EDAT- 2017/10/04 06:00
MHDA- 2018/06/26 06:00
CRDT- 2017/10/04 06:00
PHST- 2017/07/05 00:00 [received]
PHST- 2017/09/22 00:00 [revised]
PHST- 2017/09/28 00:00 [accepted]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2017/10/04 06:00 [entrez]
AID - S0161-813X(17)30203-6 [pii]
AID - 10.1016/j.neuro.2017.09.014 [doi]
PST - ppublish
SO  - Neurotoxicology. 2017 Dec;63:126-136. doi: 10.1016/j.neuro.2017.09.014. Epub 2017 
      Sep 29.