Melanin-concentrating hormone induces neurite outgrowth in human neuroblastoma SH-SY5Y cells through p53 and MAPKinase signaling pathways.
Melanin-concentrating hormone (MCH) peptide plays a major role in energy homeostasis regulation. Little is known about cellular functions engaged by endogenous MCH receptor (MCH-R1). Here, MCH-R1 mRNA and cognate protein were found expressed in human neuroblastoma SH-SY5Y cells. Electrophysiological experiments demonstrated that MCH modulated K(+) currents, an effect depending upon the time of cellular growth. MCH treatments induced a transient phosphorylation of MAPKinases, abolished by PD98059, and partially blocked by PTX, suggesting a Galphai/Galphao protein contribution. MCH stimulated expression and likely nuclear localization of phosphorylated p53 proteins, an effect fully dependent upon MAPKinase activities. MCH treatment also increased phosphorylation of Elk-1 and up-regulated Egr-1, two transcriptional factors targeted by the MAPKinase pathway. Finally, MCH provoked neurite outgrowth after 24h-treatment of neuroblastoma cells. This effect and transcriptional factors activation were partly prevented by PD98059. Collectively, our results provide the first evidence for a role of MCH in neuronal differentiation of endogenously MCH-R1-expressing cells via non-exclusive MAPKinase and p53 signaling pathways.
Cotta-Grand
Natacha
N
The Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique and Université Nice-Sophia Antipolis, Valbonne, France.
Rovère
Carole
C
Guyon
Alice
A
Cervantes
Alexandra
A
Brau
Frédéric
F
Nahon
Jean-Louis
JL
D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D007150:Immunohistochemistry; D008543:Melanins / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D010907:Pituitary Hormones / Q000494:pharmacology*; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
C497325:EGR1 protein, human; C494112:ELK1 protein, human; D051766:Early Growth Response Protein 1; D005419:Flavonoids; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D011979:Receptors, Pituitary Hormone; D016159:Tumor Suppressor Protein p53; D050807:ets-Domain Protein Elk-1; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one