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Eur J Neurosci. 2002 May;15(9):1451-60.

PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis.

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1
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France.

Abstract

Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in neuronal cell death associated with neurodegenerative diseases and stroke. In the present study, we have investigated the potential neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on oxidative stress-induced apoptosis. Incubation of cerebellar granule cells with PACAP inhibited hydrogen peroxide-evoked cell death in a concentration-dependent manner. The effect of PACAP on granule cell survival was not mimicked by vasoactive intestinal polypeptide and was blocked by the antagonist PACAP6-38. The protective action of PACAP upon hydrogen peroxide-induced neuronal cell death was abolished by the MAP-kinase kinase (MEK) inhibitor U0126 and mimicked by the caspase-3 inhibitor Z-DEVD-FMK. PACAP markedly inhibited hydrogen peroxide-evoked caspase-3 activation and DNA fragmentation. Taken together, these data indicate that PACAP, acting through PACAP receptor type 1, exerts a potent protective effect against neuronal degeneration induced by hydrogen peroxide. The anti-apoptotic effect of PACAP is mediated through the MAP-kinase pathway and can be accounted for by inhibition of caspase-3 activation resulting from oxidative stress.

[Indexed for MEDLINE]

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