D. V. and T. F. P. contributed equally to this work.
PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis
Article first published online: 22 MAY 2002
European Journal of Neuroscience
Volume 15, Issue 9, pages 1451–1460, May 2002
How to Cite
Vaudry, D., Pamantung, T. F., Basille, M., Rousselle, C., Fournier, A., Vaudry, H., Beauvillain, J. C. and Gonzalez, B. J. (2002), PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis. European Journal of Neuroscience, 15: 1451–1460. doi: 10.1046/j.1460-9568.2002.01981.x
- Issue published online: 22 MAY 2002
- Article first published online: 22 MAY 2002
- Received 25 October 2001, revised 28 January 2002, accepted 12 February 2002
- hydrogen peroxide;
- pituitary adenylate cyclase-activating polypeptide;
- vasoactive intestinal polypeptide
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.