title: Effects of PACAP on the circadian changes of signaling pathways in chicken pinealocytes.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of circadian rhythms. In mammals, the brain's biological clock is the suprachiasmatic nucleus, receiving photic information from the retina through the retinohypothalamic pathway, where PACAP is the main cotransmitter of glutamate. The primary conductor of circadian rhythms of birds is the pineal gland. The presence of PACAP has been demonstrated both in the rat and avian pineal gland, where PACAP stimulates melatonin synthesis. The signaling mechanism, by which PACAP modulates melatonin synthesis and circadian rhythmic functions of the pineal gland, is only partially known. The aim of the present study was to investigate the effects of PACAP on the changes of p38 mitogen-activated protein kinase (MAPK) and 14-3-3 protein in chick pineal cell culture both of which have been shown to participate in the regulation of rhythmic functions. Pineal cells were treated with 1, 10, or 100 nM PACAP38 every 4 h during a 24-h period. The phosphorylation of p38 MAPK showed obvious changes during the observed 24 h, while the level of 14-3-3 protein did not. We found that the lowest used dose of PACAP did not cause any phase alteration in p38 MAPK phosphorylation. Ten nM PACAP induced a 4-h-long delay and 100 nM abolished the circadian changes of p38 MAPK phosphorylation. PACAP was not effective on the level of 14-3-3 protein in the early morning hours, and only the highest tested dose (100 nM) could evoke a change in the appearance of 14-3-3 between midday and midnight hours. In summary, PACAP modulated the phosphorylation of p38 MAPK and the appearance of 14-3-3 protein in the chicken pineal cells, but these effects were dose dependent and also depended on the time of day.
authors.affiliation: Department of Surgical Research and Techniques, Medical Faculty, University of Pecs, Kodaly Z. u. 20, 7624, Pecs, Hungary. boglarka.racz@aok.pte.hu
authors.forename: Boglarka
authors.initials: B
authors.lastname: Racz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Horvath
authors.forename: Nandor
authors.initials: N
authors.lastname: Faluhelyi
authors.forename: Andras D
authors.initials: AD
authors.lastname: Nagy
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.forename: Peter
authors.initials: P
authors.lastname: Kiss
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gallyas
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.forename: Balazs
authors.initials: B
authors.lastname: Gaszner
authors.forename: Valer
authors.initials: V
authors.lastname: Csernus
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002478:Cells, Cultured; D002645:Chickens; D002940:Circadian Rhythm / Q000502:physiology*; D010870:Pineal Gland / Q000166:cytology / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D048051:p38 Mitogen-Activated Protein Kinases