DDC expression is not regulated by NFAT5 (TonEBP) in dopaminergic neural cell lines.
Animals
Aromatic-L-Amino-Acid Decarboxylases
/ genetics
Cell Line, Tumor
Dopamine
/ metabolism
Dopaminergic Neurons
/ metabolism
Down-Regulation
Heat-Shock Proteins
/ metabolism
Humans
Membrane Glycoproteins
/ metabolism
Membrane Transport Proteins
/ metabolism
Osmotic Pressure
RNA, Small Interfering
/ metabolism
Rats
Symporters
/ metabolism
Transcription Factors
/ genetics
Up-Regulation
AADC
DDC
Hypertonic stress
NFAT5
Neural dopaminergic cell lines
PC12
SH-SY5Y
TonEBP
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
05 Jun 2020
05 Jun 2020
Historique:
received:
17
07
2019
revised:
21
01
2020
accepted:
08
03
2020
pubmed:
14
3
2020
medline:
2
6
2020
entrez:
14
3
2020
Statut:
ppublish
Résumé
The nuclear factor of activated T-cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor that regulates osmoadaptive response in multiple tissues and is highly expressed in the developing central nervous system. A former study reported that NFAT5 activation through hypertonic stress increases the expression of the dopa decarboxylase enzyme (DDC), also known as aromatic-l-amino-acid decarboxylase (AADC), in human renal proximal tubule cells, leading to an increase of dopamine synthesis. In a previous study, we identified NFAT5 as a candidate gene for cocaine dependence, a complex psychiatric disorder in which dopaminergic neurotransmission plays an important role. Therefore, to test the hypothesis that NFAT5 may also affect dopamine levels in the nervous system through the regulation of DDC expression, we examined this regulation using two neural dopaminergic cell lines, SH-SY5Y and PC12. The effect of NFAT5 on the expression of the neuronal isoform of DDC was evaluated by qRT-PCR. Upon hypertonic stress, NFAT5 was activated and accumulated into the nuclei and, subsequently, the expression of NFAT5 and its known targets sodium/myo-inositol cotransporter 1 (SMIT) and sodium chloride/taurine cotransporter (TAUT) increased, as expected. However, the expression of DDC decreased. When silencing the expression of NFAT5 with a specific shRNA we observed that the downregulation of DDC is independent from NFAT5 in both cell lines and is due to hypertonic stress. In conclusion, NFAT5 does not regulate the expression of the neuronal isoform of DDC in neural dopaminergic cell lines and, consequently, it does not modulate dopamine synthesis through DDC.
Identifiants
pubmed: 32165301
pii: S0378-1119(20)30238-9
doi: 10.1016/j.gene.2020.144569
pii:
doi:
Substances chimiques
Heat-Shock Proteins
0
Membrane Glycoproteins
0
Membrane Transport Proteins
0
NFAT5 protein, human
0
RNA, Small Interfering
0
Symporters
0
Transcription Factors
0
SLC5A3 protein, human
146890-04-2
taurine transporter
148686-53-7
Aromatic-L-Amino-Acid Decarboxylases
EC 4.1.1.28
DDC protein, human
EC 4.1.1.28
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
144569Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funder Minoryx Therapeutics provided support in the form of salaries for author HD, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors declare no competing interests.