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

Autor: Masmoudi-Kouki, Olfa, Douiri, Salma, Hamdi, Yosra, Kaddour, Hadhemi, Bahdoudi, Saima, Vaudry, David, Basille, Magali, Leprince, Jérôme, Fournier, Alain, Vaudry, Hubert, Tonon, Marie-Christine, Amri, Mohamed
Přispěvatelé: Université de Tunis El Manar (UTM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
MESH: Signal Transduction
endocrine system
MESH: Rats
MESH: Mitochondria
MESH: Drug Interactions
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
MESH: Neurons
Apoptosis
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
MESH: Animals
Newborn
Cerebellum
MESH: Caspase 3
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Animals
Drug Interactions
MESH: Animals
Rats
Wistar
Cells
Cultured
Cerebral Cortex
Neurons
MESH: Glutathione
MESH: Oxidative Stress
MESH: Culture Media
Conditioned
Caspase 3
MESH: Apoptosis
MESH: Pituitary Adenylate Cyclase-Activating Polypeptide
MESH: Reactive Oxygen Species
Hydrogen Peroxide
MESH: Rats
Wistar
Glutathione
MESH: Cerebellum
MESH: Cerebral Cortex
Mitochondria
Rats
MESH: Astrocytes
Oxidative Stress
Animals
Newborn
Astrocytes
Culture Media
Conditioned
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Pituitary Adenylate Cyclase-Activating Polypeptide
MESH: Hydrogen Peroxide
Reactive Oxygen Species
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
MESH: Cells
Cultured
Zdroj: Journal of Neurochemistry
Journal of Neurochemistry, Wiley, 2011, 117 (3), pp.403-411. ⟨10.1111/j.1471-4159.2011.07185.x⟩
ISSN: 0022-3042
1471-4159
DOI: 10.1111/j.1471-4159.2011.07185.x⟩
Popis: International audience; 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 H(2)O(2)-induced astrocyte death. Pre-treatment of cultured rat astrocytes with nanomolar concentrations of PACAP prevented cell death provoked by H(2)O(2) (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 H(2)O(2)-evoked ROS accumulation and glutathione content reduction. In addition, PACAP prevented the decrease of mitochondrial activity and caspase 3 activation induced by H(2)O(2). 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.
Databáze: OpenAIRE
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