AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress.

Autor: Abid H; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Cartier D; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Hamieh A; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., François-Bellan AM; CNRS UMR 7051, Neurophysiopathol Inst, Aix-Marseille University, 13015 Marseille, France., Bucharles C; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Pothion H; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Manecka DL; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Leprince J; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Adriouch S; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France.; UNIROUEN, Inserm U1234, Pathophysiology and Biotherapy of Inflammatory and Autoimmune Diseases, Rouen-Normandie University, 76000, Rouen, France., Boyer O; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France.; UNIROUEN, Inserm U1234, Pathophysiology and Biotherapy of Inflammatory and Autoimmune Diseases, Rouen-Normandie University, 76000, Rouen, France., Anouar Y; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France., Lihrmann I; UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France. isabelle.lihrmann@univ-rouen.fr.; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France. isabelle.lihrmann@univ-rouen.fr.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2019 Jun; Vol. 56 (6), pp. 4086-4101. Date of Electronic Publication: 2018 Sep 28.
DOI: 10.1007/s12035-018-1352-x
Abstrakt: 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.
Databáze: MEDLINE
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