%0 Journal Article %T Pituitary adenylate cyclase-activating polypeptide inhibits caspase-3 activity but does not protect cerebellar granule neurons against beta-amyloid (25-35)-induced apoptosis. %+ Neuroendocrinologie cellulaire et moléculaire %+ Institut Armand Frappier (INRS-IAF) %A Vaudry, David %A Cottet-Rousselle, Cécile %A Basille, Magali %A Falluel-Morel, Anthony %A Fournier, Alain %A Vaudry, Hubert %A Gonzalez, Bruno J %Z This work was supported by grants from INSERM (U413), an INSERM-FRSQ exchange program (to AF and HV) and the Conseil Regional de Haute-Normandie. A.F.M. was a recipient of a fellowship from the Conseil Régional de Haute-Normandie (LARC-Neuroscience network) %< avec comité de lecture %@ 0167-0115 %J Regulatory Peptides %I Elsevier %V 123 %N 1-3 %P 43-9 %8 2004-12-15 %D 2004 %R 10.1016/j.regpep.2004.05.025 %M 15518892 %K β-amyloid peptide %K PACAP %K Insulin %K Apoptosis %K Granule cells %Z Life Sciences [q-bio]/ToxicologyJournal articles %X The beta-amyloid (Abeta) peptide Abeta25-35 provokes apoptosis of cerebellar granule cells through activation of caspase-3 while the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) promotes granule cell survival by inhibiting caspase-3 activation through the intrinsic apoptotic pathway. The aim of the present study was to determine whether PACAP could prevent Abeta25-35 neurotoxicity by inhibiting caspase-3 activity. A 24-h exposure of cultured cerebellar granule cells to Abeta25-35 induced shrinkage of cell bodies, neurite retraction and alteration of mitochondrial activity. Administration of graded concentrations (10-80 microM) of Abeta25-35 induced a dose-related decrease of the number of living cells, and the neurotoxic effect was highly significant after a 24-h exposure to 80 microM Abeta25-35. Exposure of cerebellar granule cells to Abeta25-35 markedly enhanced caspase-3 but not caspase-9 activity. Co-incubation with 1 microM PACAP significantly reduced Abeta25-35-evoked caspase-3 activation. In contrast, PACAP did not prevent the deleterious effects of Abeta25-35 on mitochondrial potential and granule cell survival. Taken together, these data suggest that caspase-3 activation is not the main pathway activated by Abeta25-35 that leads to granule cell death. The results also demonstrate that PACAP cannot be considered as a potent neuroprotective factor against Abeta25-35-induced apoptosis in cerebellar granule neurons. %G English %L pasteur-00820042 %U https://riip.hal.science/pasteur-00820042 %~ RIIP %~ INRS-IAF %~ COMUE-NORMANDIE %~ UNIROUEN