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Davunetide (NAP) Protects the Retina Against Early Diabetic Injury by Reducing Apoptotic Death

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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.

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Acknowledgments

Dr. Soraya Scuderi and Agata Grazia D’Amico were supported by the International PhD Program in Neuropharmacology, Medical School, University of Catania, Catania, Italy. The study was supported by the Ministry of University and Research, grant PRIN 2009BM7LJC_005 and grant PON 01-00110. These experiments were also accomplished using equipment provided by the city hall of Catania (ICT-E1 project). We thank Mr. P. Asero for his technical support.

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Authors and Affiliations

  1. Department of Bio-Medical Sciences, Section of Anatomy and Histology, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy

    Soraya Scuderi, Agata Grazia D’Amico, Alessandro Castorina & Velia D’Agata

  2. Department of Biological, Geological and Environmental Sciences, Section of Animal Biology, University of Catania, Catania, Italy

    Concetta Federico

  3. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy

    Giuseppina Marrazzo, Filippo Drago & Claudio Bucolo

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  1. Soraya Scuderi
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  2. Agata Grazia D’Amico
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  3. Alessandro Castorina
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  4. Concetta Federico
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  5. Giuseppina Marrazzo
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  6. Filippo Drago
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  8. Velia D’Agata
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Correspondence to Velia D’Agata.

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Scuderi, S., D’Amico, A.G., Castorina, A. et al. Davunetide (NAP) Protects the Retina Against Early Diabetic Injury by Reducing Apoptotic Death. J Mol Neurosci 54, 395–404 (2014). https://doi.org/10.1007/s12031-014-0244-4

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  • DOI: https://doi.org/10.1007/s12031-014-0244-4

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