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Growth hormone‐releasing peptide 6 protection of hypothalamic neurons from glutamate excitotoxicity is caspase independent and not mediated by insulin‐like growth factor I
Author(s) -
DelgadoRubín A.,
Chowen Julie A.,
Argente Jesús,
Frago Laura M.
Publication year - 2009
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.06770.x
Subject(s) - excitotoxicity , neuroprotection , glutamate receptor , programmed cell death , growth factor , insulin like growth factor , microbiology and biotechnology , biology , caspase , apoptosis , medicine , endocrinology , chemistry , receptor , pharmacology , biochemistry
Treatment of the fetal hypothalamic neuronal cell line RCA‐6 with growth hormone‐releasing peptide 6, an agonist of the ghrelin receptor, or insulin‐like growth factor I activates intracellular signalling cascades associated with anti‐apoptotic actions. Abnormally high concentrations of glutamate provoke over‐excitation of neurons leading to cell damage and apoptosis. Thus, the aim of this study was to investigate whether the administration of growth hormone‐releasing peptide 6 and insulin‐like growth factor I attenuates monosodium glutamate‐induced apoptosis in RCA‐6 neurons and the mechanisms involved. Two different mechanisms are involved in glutamate‐induced cell death, one by means of caspase activation and the second through activation of a caspase‐independent pathway of apoptosis mediated by the translocation of apoptosis‐inducing factor. Growth hormone‐releasing peptide 6 partially reversed glutamate‐induced cell death but not the activation of caspases, suggesting blockage of the caspase‐independent cell death pathway, which included interference with the translocation of apoptosis‐inducing factor to the nucleus associated with the induction of Bcl‐2. In contrast, the addition of insulin‐like growth factor I to RCA‐6 neurons abolished glutamate‐induced caspase activation and cell death. These data demonstrate for the first time a neuroprotective role for growth hormone secretagogues in the caspase‐independent cell death pathway and indicate that these peptides have neuroprotective effects independent of its induction of insulin‐like growth factor I.