AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress.
AMP-Activated Protein Kinases
/ metabolism
Animals
Cell Differentiation
/ drug effects
Cell Survival
/ drug effects
Enzyme Activation
/ drug effects
HEK293 Cells
Humans
Models, Biological
Neuroendocrine Cells
/ cytology
Nuclear Respiratory Factor 1
/ metabolism
Oxidative Stress
/ drug effects
PC12 Cells
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ metabolism
Pituitary Adenylate Cyclase-Activating Polypeptide
/ pharmacology
Protein Binding
/ drug effects
Rats
Selenoproteins
/ genetics
Transcription, Genetic
/ drug effects
Mitochondriogenesis
NRF-1
Oxidative stress
PGC-1α
cAMP
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
13
07
2018
accepted:
13
09
2018
pubmed:
30
9
2018
medline:
30
8
2019
entrez:
30
9
2018
Statut:
ppublish
Résumé
Several cues including pituitary adenylate cyclase-activating polypeptide (PACAP), which acts through cAMP stimulation, specify the conversion of sympathoadrenal (SA) precursors toward different cell phenotypes by promoting their survival and differentiation. Selenoprotein T (SELENOT) is a PACAP-stimulated ER oxidoreductase that exerts an essential antioxidant activity and whose up-regulation is associated with SA cell differentiation. In the present study, we investigated the transcriptional cascade elicited by PACAP/cAMP to trigger SELENOT gene transcription during the conversion of PC12 cells from SA progenitor-like cells toward a neuroendocrine phenotype. Unexpectedly, we found that PACAP/cAMP recruits the canonical pathway that regulates mitochondrial function in order to elicit SELENOT gene transcription and the consequent antioxidant response during PC12 cell differentiation. This cascade involves LKB1-mediated AMPK activation in order to stimulate SELENOT gene transcription through the PGC1-α/NRF-1 complex, thus allowing SELENOT to promote PACAP-stimulated neuroendocrine cell survival and differentiation. Our data reveal that a PACAP and cAMP-activated AMPK-PGC-1α/NRF-1 cascade is critical for the coupling of oxidative stress tolerance, via SELENOT gene expression, and mitochondrial biogenesis in order to achieve PC12 cell differentiation. The data further highlight the essential role of SELENOT in cell metabolism during differentiation.
Identifiants
pubmed: 30267375
doi: 10.1007/s12035-018-1352-x
pii: 10.1007/s12035-018-1352-x
doi:
Substances chimiques
Nuclear Respiratory Factor 1
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Ppargc1a protein, rat
0
Selenoproteins
0
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4086-4101Références
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