title: Molecular mechanisms underlying the Nephroprotective effects of PACAP in diabetes.
abstract: Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30-40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.
authors.affiliation: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pécs, 7624, Pécs, Szigeti u 12, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Banki
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kovacs
authors.forename: Daniel
authors.initials: D
authors.lastname: Nagy
authors.forename: Tamas
authors.initials: T
authors.lastname: Juhasz
authors.forename: Peter
authors.initials: P
authors.lastname: Degrell
authors.forename: Katalin
authors.initials: K
authors.lastname: Csanaky
authors.forename: Peter
authors.initials: P
authors.lastname: Kiss
authors.forename: Gabor
authors.initials: G
authors.lastname: Jancso
authors.forename: Gabor
authors.initials: G
authors.lastname: Toth
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D016328:NF-kappa B; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D053773:Transforming Growth Factor beta1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005978:Glutathione