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Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells.

Artikel i vetenskaplig tidskrift
Författare Inger Johansson
Silvia Destefanis
N David Åberg
Maria A I Åberg
Klas Blomgren
Changlian Zhu
Corrado Ghè
Riccarda Granata
Ezio Ghigo
Giampiero Muccioli
Peter S Eriksson
Jörgen Isgaard
Publicerad i Endocrinology
Volym 149
Nummer/häfte 5
Sidor 2191-9
ISSN 0013-7227
Publiceringsår 2008
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Institutionen för medicin, avdelningen för invärtesmedicin
Institutionen för kliniska vetenskaper
Sidor 2191-9
Språk en
Länkar dx.doi.org/10.1210/en.2007-0733
Ämnesord 1-Phosphatidylinositol 3-Kinase, metabolism, Animals, Cell Proliferation, drug effects, Cells, Cultured, Cytoprotection, drug effects, Ghrelin, analogs & derivatives, pharmacology, Growth Hormone, secretion, Growth Hormone-Releasing Hormone, analogs & derivatives, Hippocampus, drug effects, metabolism, pathology, physiology, Mitogen-Activated Protein Kinase 1, metabolism, Mitogen-Activated Protein Kinase 3, metabolism, Necrosis, Oligopeptides, pharmacology, Oncogene Protein v-akt, metabolism, Rats, Receptors, Ghrelin, metabolism, Signal Transduction, drug effects, Stem Cells, drug effects, pathology, physiology
Ämneskategorier Dermatologi och venereologi, Endokrinologi

Sammanfattning

Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.

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