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Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

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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.

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Acknowledgments

This study was supported by OTKA K104984, 108596, PD109644, TAMOP 4.2.2.A-11/1/KONV-2012-0024, Arimura Foundation and PTE-MTA “Lendület” Program, Bolyai Scholarship. This research was realized in the frames of TAMOP 4.2.4. A/2-11-1-2012-0001 “National Excellence Program—Elaborating and operating an inland student and researcher personal support system convergence program”. The project was subsidized by the European Union and co-financed by the European Social Fund.

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Authors and Affiliations

  1. Department of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pécs, 7624, Pécs, Szigeti u 12, Hungary

    Eszter Banki, Daniel Nagy, Katalin Csanaky, Peter Kiss, Andrea Tamas & Dora Reglodi

  2. Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary

    Krisztina Kovacs

  3. Department of Pharmacology and Pharmacotherapy, University of Pécs, Pécs, Hungary

    Daniel Nagy

  4. Department of Anatomy, Histology and Embryology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Tamas Juhasz

  5. Internal Medicine 2/ Nephrology Center, University of Pécs, Pécs, Hungary

    Peter Degrell

  6. Surgical Research and Techniques, University of Pécs, Pécs, Hungary

    Gabor Jancso

  7. Department of Medical Chemistry, University of Szeged, Szeged, Hungary

    Gabor Toth

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  1. Eszter Banki
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  2. Krisztina Kovacs
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  4. Tamas Juhasz
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  9. Gabor Toth
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  10. Andrea Tamas
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  11. Dora Reglodi
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Correspondence to Dora Reglodi.

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Banki, E., Kovacs, K., Nagy, D. et al. Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes. J Mol Neurosci 54, 300–309 (2014). https://doi.org/10.1007/s12031-014-0249-z

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