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Davunetide (NAP) protects the retina against early diabetic injury by reducing apoptotic death.

Abstract
Davunetide (NAP) is an eight amino acid peptide that has been shown to provide potent neuroprotection. In the present study, we investigated the neuroprotective effect of NAP in diabetic retinopathy using an in vivo streptozotocin (STZ)-induced diabetic model. A single intraocular injection of NAP (100 μg/mL) or vehicle was administered 1 week after STZ injection. Three weeks after diabetes induction, we assessed the retinal expression and distribution of apoptosis markers, cleaved caspase-3, and Bcl2, by Western blot and immunofluorescent analysis. Furthermore, we evaluated the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) and/or phosphatidylinositol-3 kinase/Akt pathways by measuring the protein levels of p-ERK and p-AKT with or without NAP treatment. Results demonstrated that NAP treatment reduced apoptotic event in diabetic retina, and it restored cleaved caspase-3 expression levels in the retina of STZ-injected rats as well as the decreased Bcl2. NAP treatment improved cellular survival through the activation of the MAPK/ERK pathway. Taken together, these findings suggested that NAP might be useful to treat retinal degenerative diseases.
AuthorsSoraya Scuderi, Agata Grazia D'Amico, Alessandro Castorina, Concetta Federico, Giuseppina Marrazzo, Filippo Drago, Claudio Bucolo, Velia D'Agata
JournalJournal of molecular neuroscience : MN (J Mol Neurosci) Vol. 54 Issue 3 Pg. 395-404 (Nov 2014) ISSN: 1559-1166 [Electronic] United States
PMID24488575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Oligopeptides
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • davunetide
Topics
  • Animals
  • Apoptosis
  • Diabetic Retinopathy (drug therapy, metabolism)
  • MAP Kinase Signaling System
  • Male
  • Oligopeptides (pharmacology, therapeutic use)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Retina (drug effects, metabolism)

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