title: Mice deficient in pituitary adenylate cyclase activating polypeptide display increased sensitivity to renal oxidative stress in vitro.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, showing widespread occurrence in the nervous system and also in peripheral organs. The neuroprotective effects of PACAP are well-established in different neuronal systems against noxious stimuli in vitro and in vivo. Recently, its general cytoprotective actions have been recognized, including renoprotective effects. However, the effect of endogenous PACAP in the kidneys is not known. The main aim of the present study was to investigate whether the lack of this endogenous neuropeptide influences survival of kidney cells against oxidative stress. First, we determined the presence of endogenous PACAP from mouse kidney homogenates by mass spectrometry and PACAP-like immunoreactivity by radioimmunoassay. Second, primary cultures were isolated from wild type and PACAP deficient mice and cell viability was assessed following oxidative stress induced by 0.5, 1.5 and 3mM H(2)O(2). Our mass spectrometry and radioimmunoassay results show that PACAP is endogenously present in the kidney. The main part of our study revealed that the sensitivity of cells from PACAP deficient mice was increased to oxidative stress: both after 2 or 4h of exposure, cell viability was significantly reduced compared to that from control wild type mice. This increased sensitivity of kidneys from PACAP deficient mice could be counteracted by exogenously given PACAP38. These results show, for the first time, that endogenous PACAP protects against oxidative stress in the kidney, and that PACAP may act as a stress sensor in renal cells. These findings further support the general cytoprotective nature of this neuropeptide.
authors.affiliation: Department of Anatomy, University of Pecs, Pecs, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Horvath
authors.forename: Laszlo
authors.initials: L
authors.lastname: Mark
authors.forename: Reka
authors.initials: R
authors.lastname: Brubel
authors.forename: Peter
authors.initials: P
authors.lastname: Szakaly
authors.forename: Boglarka
authors.initials: B
authors.lastname: Racz
authors.forename: Peter
authors.initials: P
authors.lastname: Kiss
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
authors.forename: Andrea
authors.initials: A
authors.lastname: Lubics
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.forename: Gergely
authors.initials: G
authors.lastname: Furjes
authors.forename: Jozsef
authors.initials: J
authors.lastname: Nemeth
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
mesh_terms: D000818:Animals; D002470:Cell Survival; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D011863:Radioimmunoassay
chemical_list: C495402:Adcyap1 protein, mouse; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D006861:Hydrogen Peroxide