Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

Eszter Banki, Krisztina Kovacs, Daniel Nagy, Tamas Juhasz, Peter Degrell, Katalin Csanaky, P. Kiss, Gabor Jancso, G. Tóth, A. Tamás, D. Reglodi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Molecular Neuroscience
DOIs
Publication statusAccepted/In press - 2014

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
Kidney
Diabetic Nephropathies
Neuropeptides
Caspase 3
Chronic Kidney Failure
Glutathione
Anti-Inflammatory Agents
Collagen
Therapeutics
Down-Regulation
Antioxidants
Western Blotting
Transplants
Polymerase Chain Reaction
Proteins

Keywords

  • Apoptosis
  • Diabetes
  • Kidney
  • Oxidative stress
  • PACAP

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes. / Banki, Eszter; Kovacs, Krisztina; Nagy, Daniel; Juhasz, Tamas; Degrell, Peter; Csanaky, Katalin; Kiss, P.; Jancso, Gabor; Tóth, G.; Tamás, A.; Reglodi, D.

In: Journal of Molecular Neuroscience, 2014, p. 1-10.

Research output: Contribution to journalArticle

Banki, Eszter ; Kovacs, Krisztina ; Nagy, Daniel ; Juhasz, Tamas ; Degrell, Peter ; Csanaky, Katalin ; Kiss, P. ; Jancso, Gabor ; Tóth, G. ; Tamás, A. ; Reglodi, D. / Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes. In: Journal of Molecular Neuroscience. 2014 ; pp. 1-10.
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