title: Peroxiredoxin 2 is involved in the neuroprotective effects of PACAP in cultured cerebellar granule neurons.
abstract: The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is known to counteract in vitro the deleterious effects of toxic agents on cerebellar granule cell survival and differentiation. The potent antiapoptotic action of PACAP is mediated through inhibition of caspase-3 activity; however, additional proteins are likely involved and remain to be identified. Two-dimensional gel electrophoresis analysis coupled with mass spectrometry characterization led to the identification of a protein, peroxiredoxin 2, which was induced after a 6-h treatment with PACAP. Western blot analysis confirmed the regulation of peroxiredoxin 2 by PACAP and revealed that this protein is induced by both cyclic AMP and protein kinase C stimulators. Inhibition of peroxiredoxin 2 expression, using two distinct small-interfering RNAs (siRNAs), reduced the effect of PACAP on caspase-3 activity and cerebellar granule cell survival. Peroxiredoxin 2 expression was also induced in vivo and in vitro by ethanol. Although ethanol and PACAP exert opposite effects on caspase-3 activity, inhibition of peroxiredoxin 2 expression, using siRNAs, only reduced the ability of PACAP to prevent ethanol-induced caspase-3 activity. Taken together, these data indicate that peroxiredoxin 2 is probably involved in the neurotrophic effect of PACAP and suggest that this protein may have a therapeutic potential for the treatment of some neurodegenerative diseases.
authors.affiliation: INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, 76821, Mont-Saint-Aignan, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Botia
authors.forename: Damien
authors.initials: D
authors.lastname: Seyer
authors.forename: Aurélia
authors.initials: A
authors.lastname: Ravni
authors.forename: Magalie
authors.initials: M
authors.lastname: Bénard
authors.forename: Anthony
authors.initials: A
authors.lastname: Falluel-Morel
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouenne
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Gonzalez
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D005576:Colforsin / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D034741:RNA, Small Interfering; D005576:Colforsin; D000431:Ethanol; D054464:Peroxiredoxins; D053148:Caspase 3; D013755:Tetradecanoylphorbol Acetate