Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y.

Détails

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Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_A51A4B4FD3EB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glial-derived neurotrophic factor modulates enteric neuronal survival and proliferation through neuropeptide Y.
Périodique
Gastroenterology
Auteur⸱e⸱s
Anitha M., Chandrasekharan B., Salgado J.R., Grouzmann E., Mwangi S., Sitaraman S.V., Srinivasan S.
ISSN
0016-5085 (Print)
ISSN-L
0016-5085
Statut éditorial
Publié
Date de publication
10/2006
Peer-reviewed
Oui
Volume
131
Numéro
4
Pages
1164-1178
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
BACKGROUND & AIMS: Glial-derived neurotrophic factor (GDNF) promotes the survival and proliferation of enteric neurons. Neuropeptide Y (NPY) is an important peptide regulating gastrointestinal motility. The role of NPY on the survival and proliferation of enteric neurons is not known. We examined the effects of GDNF on the expression and release of NPY from enteric neurons and the role of NPY in promoting enteric neuronal proliferation and survival.
METHODS: Studies were performed in primary enteric neuronal cultures and NPY knockout mice (NPY(-/-)). GDNF-induced expression of NPY was assessed by reverse-transcription polymerase chain reaction (RT-PCR), immunocytochemistry, and enzyme-linked immunosorbent assay. Using NPY-siRNA and NPY-Y1 receptor antagonist, we examined the role of NPY in mediating the survival and proliferation effects of GDNF. Gastrointestinal motility was assessed by measuring gastric emptying, intestinal transit, and isometric muscle recording from intestinal muscle strips.
RESULTS: GDNF induced a significant increase in NPY messenger RNA and protein expression in primary enteric neurons and the release of NPY into the culture medium. NPY (1 mumol/L) significantly increased proliferation of neurons and reduced apoptosis. In the presence of NPY-siRNA and NPY-Y1 receptor antagonist or in enteric neurons cultured from NPY(-/-) mice, GDNF-mediated neuronal proliferation and survival was reduced. NPY increased the phosphorylation of Akt, a downstream target of the PI-3-kinase pathway. In NPY(-/-) mice, there were significantly fewer nNOS-containing enteric neurons compared with wild-type (WT) mice. NPY(-/-) mice had accelerated gastric emptying and delayed intestinal transit compared with WT mice.
CONCLUSIONS: We demonstrate that NPY acts as an autocrine neurotrophic factor for enteric neurons.
Mots-clé
Animals, Apoptosis/drug effects, Apoptosis/physiology, Cell Division/drug effects, Cell Division/physiology, Cell Survival/drug effects, Cell Survival/physiology, Cells, Cultured, Chromones/pharmacology, Electric Stimulation, Enzyme Inhibitors/pharmacology, Gastric Emptying/physiology, Gastrointestinal Motility/physiology, Glial Cell Line-Derived Neurotrophic Factor/metabolism, Glial Cell Line-Derived Neurotrophic Factor/pharmacology, Intestines/innervation, Intestines/physiology, Mice, Mice, Knockout, Morpholines/pharmacology, Muscle Relaxation/physiology, Muscle, Smooth/innervation, Muscle, Smooth/physiology, Myenteric Plexus/cytology, Myenteric Plexus/physiology, Neurons/cytology, Neuropeptide Y/genetics, Neuropeptide Y/metabolism, Nitric Oxide Synthase Type I/metabolism, Phosphatidylinositol 3-Kinases/antagonists & inhibitors, Phosphatidylinositol 3-Kinases/metabolism, Proto-Oncogene Proteins c-akt/metabolism, RNA, Messenger/metabolism, Rats, Rats, Sprague-Dawley, Receptors, Neuropeptide Y/antagonists & inhibitors, Receptors, Neuropeptide Y/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 10:55
Dernière modification de la notice
20/08/2019 15:10
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