title: Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis.
abstract: Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. Many factors that inhibit cell death have been identified, but the mechanisms involved are not always fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neuroprotective activities during development. PACAP also inhibits apoptosis in cardiomyopathy, decreases glutamate-induced retinal injury, reduces neuronal loss in case of stroke, and prevents ethanol neurotoxicity. Most of the antiapoptotic effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression which inhibits cytochrome c release and blocks in turn caspase activation. PACAP also acts through the PI3K/Akt pathway and inhibits the expression of proapoptotic factors such as c-Jun or Bax. The remarkable effect of PACAP on the apoptotic cascade suggests that innovative PACAP derivatives could potentially be useful for treatment of post-traumatic lesions, chronic neurodegenerative diseases, cardiac ischemia and/or retinopathy.
authors.affiliation: Department of Pediatrics, Laval University, St-François d’Assise Hospital Research Center, Québec, Canada.
authors.forename: Tommy
authors.initials: T
authors.lastname: Seaborn
authors.forename: Olfa
authors.initials: O
authors.lastname: Masmoudi-Kouli
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology* / Q000502:physiology*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D053148:Caspase 3