Pituitary adenylate cyclase‐activating polypeptide protects astroglial cells against oxidative stress‐induced apoptosis

• Published in: Journal of neurochemistry 2011-05, Vol.117 (3), p.403-411
• Main Authors: Masmoudi‐Kouki, Olfa, Douiri, Salma, Hamdi, Yosra, Kaddour, Hadhémi, Bahdoudi, Saima, Vaudry, David, Basille, Magali, Leprince, Jérôme, Fournier, Alain, Vaudry, Hubert, Tonon, Marie‐Christine, Amri, Mohamed
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis; Apoptosis - drug effects; Astrocytes; Astrocytes - chemistry; Astrocytes - drug effects; Caspase 3; Caspase 3 - metabolism; Cell Behavior; Cells; Cells, Cultured; Cellular Biology; Cerebellum; Cerebellum - cytology; Cerebral Cortex; Cerebral Cortex - cytology; Chemical Sciences; Culture Media, Conditioned; Culture Media, Conditioned - pharmacology; Drug Interactions; Glutathione; Glutathione - metabolism; Hydrogen Peroxide; Hydrogen Peroxide - pharmacology; Life Sciences; Medicinal Chemistry; Mitochondria; Mitochondria - drug effects; Neurobiology; Neurons; Neurons - drug effects; Neurons and Cognition; Oxidative Stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; PACAP; Pharmaceutical sciences; Pharmacology; Pituitary Adenylate Cyclase-Activating Polypeptide; Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology; Pituitary gland; Polypeptides; Rats; Rats, Wistar; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; Signal Transduction; Signal Transduction - drug effects; Stress
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07185.x

J. Neurochem. (2011) 117, 403–411. Oxidative stress, associated with a variety of disorders including neurodegenerative diseases, results from accumulation of reactive oxygen species (ROS). Oxidative stress is not only responsible for neuron apoptosis, but can also provoke astroglial cell death. Numerous studies indicate that pituitary adenylate cyclase‐activating polypeptide (PACAP) promotes neuron survival, but nothing is known regarding the action of PACAP on astroglial cell survival. Thus, the purpose of the present study was to investigate the potential glioprotective effect of PACAP on H2O2‐induced astrocyte death. Pre‐treatment of cultured rat astrocytes with nanomolar concentrations of PACAP prevented cell death provoked by H2O2 (300 μM), whereas vasoactive intestinal polypeptide was devoid of protective activity. The effect of PACAP on astroglial cell survival was abolished by the type 1 PACAP receptor antagonist, PACAP6‐38. The protective action of PACAP was blocked by the protein kinase A inhibitor H89, the protein kinase C inhibitor chelerythrine and the mitogen‐activated protein (MAP)‐kinase kinase (MEK) inhibitor U0126. PACAP stimulated glutathione formation, and blocked H2O2‐evoked ROS accumulation and glutathione content reduction. In addition, PACAP prevented the decrease of mitochondrial activity and caspase 3 activation induced by H2O2. Taken together, these data indicate for the first time that PACAP, acting through type 1 PACAP receptor, exerts a potent protective effect against oxidative stress‐induced astrocyte death. The anti‐apoptotic activity of PACAP on astrocytes is mediated through the protein kinase A, protein kinase C and MAPK transduction pathways, and can be accounted for by inhibition of ROS‐induced mitochondrial dysfunctions and caspase 3 activation.