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CEPO (carbamylated erythropoietin)-Fc protects hippocampal cells in culture against beta amyloid-induced apoptosis: considering Akt/GSK-3β and ERK signaling pathways

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Abstract

The tissue-protective properties of erythropoietin (EPO) have been described in several neurodegenerative diseases models, but erythrocytosis following EPO treatment may lead to deleterious effects. Carbamylated erythropoietin, an EPO derivative lacking hematopoietic side effects, has shown protective properties in some studies. However, it is not known if CEPO protects primary hippocampal cells against Aβ25−35 toxicity. The present study aimed to investigate the effect of CEPO-Fc on biochemical alterations in Akt, GSK-3β, and ERK signaling and cell death induced by Aβ25−35 in isolated hippocampal cell culture. The embryonic hippocampal cells were obtained from 18–19 day rat embryos. The cells were exposed with Aβ25−35 (20 µM) in the absence or presence of CEPO-Fc (1 or 5 IU) and PI3k and ERK inhibitors. CEPO-Fc at the dose of 5 IU significantly prevented the cell loss and caspase-3 cleavage caused by Aβ25−35. Additionally, CEPO-Fc noticeably reversed Aβ mediated decrement of Akt and GSK-3β phosphorylation. With exposure to LY294002, PI3 kinase inhibitor, Akt phosphorylation diminished and CEPO-Fc protective effects disappeared. Furthermore, while CEPO-Fc nullified Aβ-induced increment of phospho-ERK, inhibition of ERK activity by PD98059, had no effect on Aβ25−35-mediated caspase-3 cleavage and cell toxicity. These results imply that protective effects of CEPO-Fc seem to be mainly exerted through the PI3K/Akt pathway rather than ERK signaling. This study suggested that CEPO-Fc prevents Aβ-induced cell toxicity as well as Akt/GSK-3β and ERK alterations in isolated hippocampal cells. These findings might provide a new perspective on CEPO-Fc protective properties as a prospective remedial factor for neurodegenerative diseases like AD.

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  • 20 May 2020

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Acknowledgements

This article is a part of the thesis written by Mrs "Etrat Hooshmandi" in School of Medicine (Registration No: 558) and supported by a Grant (No. 22534) from Deputy of research and technology and Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Etrat Hooshmandi & Nader Maghsoudi

  2. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Etrat Hooshmandi

  3. Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical sciences, Shiraz, Iran

    Maryam Moosavi

  4. Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria

    Hermann Katinger

  5. Biology Department, University of Tehran, Tehran, Iran

    Shima Sardab

  6. Neurophysiology Research Center and Physiology department, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Rasoul Ghasemi

  7. Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nader Maghsoudi

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Hooshmandi, E., Moosavi, M., Katinger, H. et al. CEPO (carbamylated erythropoietin)-Fc protects hippocampal cells in culture against beta amyloid-induced apoptosis: considering Akt/GSK-3β and ERK signaling pathways. Mol Biol Rep 47, 2097–2108 (2020). https://doi.org/10.1007/s11033-020-05309-6

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