Melanin-concentrating hormone induces neurite outgrowth in human neuroblastoma SH-SY5Y cells through p53 and MAPKinase signaling pathways. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Peptides Année : 2009

Melanin-concentrating hormone induces neurite outgrowth in human neuroblastoma SH-SY5Y cells through p53 and MAPKinase signaling pathways.

Résumé

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.

Dates et versions

hal-00419253 , version 1 (23-09-2009)

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Natacha Cotta-Grand, Carole Rovère, Alice Guyon, Alexandra Cervantes, Frédéric Brau, et al.. Melanin-concentrating hormone induces neurite outgrowth in human neuroblastoma SH-SY5Y cells through p53 and MAPKinase signaling pathways.. Peptides, 2009, epub ahead of print. ⟨10.1016/j.peptides.2009.06.015⟩. ⟨hal-00419253⟩
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