Carbamoylated erythropoietin induces a neurotrophic gene profile in neuronal cells.
Animals
Cell Differentiation
Erythropoietin
/ pharmacology
Gene Expression Profiling
Gene Expression Regulation
/ drug effects
Laser Capture Microdissection
Male
Microarray Analysis
Nerve Growth Factors
/ genetics
Nerve Tissue Proteins
/ genetics
Nervous System
/ drug effects
Neurons
/ drug effects
PC12 Cells
Protein Carbamylation
Rats
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Antidepressant
CREB signaling
Cognition
Gene regulation
Neurotrophic signaling
PC-12
Journal
Progress in neuro-psychopharmacology & biological psychiatry
ISSN: 1878-4216
Titre abrégé: Prog Neuropsychopharmacol Biol Psychiatry
Pays: England
ID NLM: 8211617
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
23
02
2018
revised:
21
06
2018
accepted:
10
07
2018
pubmed:
19
7
2018
medline:
19
3
2019
entrez:
19
7
2018
Statut:
ppublish
Résumé
Erythropoietin (EPO), a cytokine molecule, is best-known for its role in erythropoiesis. Preclinical studies have demonstrated that EPO has robust neuroprotective effects that appear to be independent of erythropoiesis. It is also being clinically tested for the treatment of neuropsychiatric illnesses due to its behavioral actions. A major limitation of EPO is that long-term administration results in excessive red blood cell production and increased blood viscosity. A chemical modification of EPO, carbamoylated erythropoietin (CEPO), reproduces the behavioral response of EPO in animal models but does not stimulate erythropoiesis. The molecular mechanisms involved in the behavioral effects of CEPO are not known. To obtain molecular insight we examined CEPO induced gene expression in neuronal cells. PC-12 cells were treated with CEPO followed by genome-wide microarray analysis. We investigated the functional significance of the gene profile by unbiased bioinformatics analysis. The Ingenuity pathway analysis (IPA) software was employed. The results revealed activation of functions such as neuronal number and long-term potentiation. Regulated signaling cascades included categories such as neurotrophin, CREB, NGF and synaptic long-term potentiation signaling. Some of the regulated genes from these pathways are CAMKII, EGR1, FOS, GRIN1, KIF1B, NOTCH1. We also comparatively examined EPO and CEPO-induced gene expression for a subset of genes in the rat dentate gyrus. The CEPO gene profile shows the induction of genes and signaling cascades that have roles in neurogenesis and memory formation, mechanisms that can produce antidepressant and cognitive function enhancing activity.
Identifiants
pubmed: 30017780
pii: S0278-5846(18)30122-2
doi: 10.1016/j.pnpbp.2018.07.011
pmc: PMC6267980
mid: NIHMS1500320
pii:
doi:
Substances chimiques
Nerve Growth Factors
0
Nerve Tissue Proteins
0
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
132-141Subventions
Organisme : NIMH NIH HHS
ID : R01 MH106640
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115458
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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