Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

Eszter Banki, Krisztina Kovacs, Daniel Nagy, Tamas Juhasz, Peter Degrell, Katalin Csanaky, Peter Kiss, Gabor Jancso, Gabor Toth, Andrea Tamas, Dora 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)300-309
Number of pages10
JournalJournal of Molecular Neuroscience
Volume54
Issue number3
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • Apoptosis
  • Diabetes
  • Kidney
  • Oxidative stress
  • PACAP

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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