CEPO (carbamylated erythropoietin)-Fc protects hippocampal cells in culture against beta amyloid-induced apoptosis: considering Akt/GSK-3β and ERK signaling pathways
Authors: Rasoul Ghasemi
Maryam Moosavi
Hermann Katinger
Etrat Hooshmandi
Nader Maghsoudi
Shima Sardab
Journal: Molecular Biology Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Akt/GSK-3β; Beta amyloid; Carbamylated erythropoietin-Fc; Caspase-3; ERK
Affiliations: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran., Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical sciences, Shiraz, Iran., Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria., Biology Department, University of Tehran, Tehran, Iran., Neurophysiology Research Center and Physiology department, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ., Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ., Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .

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. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: The Ab20uM panel appears to show an overlap with the Ab+LY panel. ![file] , 
 Correction, May 2020: https: link.springer.com article 10.1007 s11033-020-05516-1  Unfortunately, the original version of this article contained a mistake in the arrangement of representative cell images in Fig. 2. In this figure, the same representative image for Au03b2 group was mistakenly placed for Au03b2u2009+u2009LY group. The corrected form of Fig. 2 is provided in this correction. I thank the authors and journal for addressing this duplication. ,