title: Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney.
authors.affiliation: Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Laszlo
authors.affiliation: Department of Surgery, University of Pecs, Pecs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Varga
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Kovacs
authors.affiliation: Department of Surgical Research and Techniques, University of Pecs, Pecs, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Jancso
authors.affiliation: Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Kiss
authors.affiliation: Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Tamas
authors.affiliation: Department of Surgery, University of Pecs, Pecs, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Szakaly
authors.affiliation: Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Fulop
authors.affiliation: Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary. Electronic address: dora.reglodi@aok.pte.hu.
authors.forename: D
authors.initials: D
authors.lastname: Reglodi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D006579:Heterozygote; D006720:Homozygote; D007249:Inflammation; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics* / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C495402:Adcyap1 protein, mouse; D000975:Antioxidants; D016207:Cytokines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases