Growth hormone releasing peptide-6 acts as a survival factor in glutamate-induced excitotoxicity.
Chronic systemic treatment given to adult male rats with growth hormone releasing peptide-6, an agonist of the ghrelin receptor, increases insulin-like growth factor I levels in various brain regions, including the hypothalamus and cerebellum. Furthermore, intracellular signalling cascades normally associated with anti-apoptotic actions are activated in the same areas and are coincident with decreased basal cell death. Because abnormally high concentrations of glutamate can lead to overexcitation of neurones leading to cell damage and/or death, we investigated whether administration of growth hormone releasing peptide-6 attenuates monosodium glutamate-induced apoptosis in the rat hypothalamus and cerebellum. Glutamate increased activation of caspase 9 followed by cleavage of caspase 7, which in turn fragmented poly(ADP-ribose) polymerase, terminating in cell death in both the hypothalamus and cerebellum. Growth hormone releasing peptide-6 reversed glutamate-induced cell death by decreasing activation of caspases 9 and 7 and poly(ADP-ribose) polymerase fragmentation. These results provide a better understanding of the neuroprotective role of growth hormone secretagogues and the mechanisms involved.
Delgado-Rubín de Célix
Arancha
A
Universidad Autónoma de Madrid. Departament of Pediatrics. Hospital Infantil Universitario Niño Jesús, Departament of Endocrinology, Madrid, Spain.
Chowen
Julie A
JA
Argente
Jesús
J
Frago
Laura M
LM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000633:toxicity*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology*; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D017362:Cyclic AMP Response Element-Binding Protein; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009498:Neurotoxins; D009842:Oligopeptides; D009930:Organic Chemicals; C435731:fluoro jade; D018698:Glutamic Acid; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D053179:Caspase 7