EV-3, an endogenous human erythropoietin isoform with distinct functional relevance
Abstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03167-0 |
| _version_ | 1818851582167482368 |
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| author | Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber |
| author_facet | Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber |
| author_sort | Christel Bonnas |
| collection | DOAJ |
| description | Abstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO. |
| first_indexed | 2024-12-19T07:07:19Z |
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| id | doaj.art-a3a06994804a476ea95d8d6d579490d7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T07:07:19Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a3a06994804a476ea95d8d6d579490d72022-12-21T20:31:15ZengNature PortfolioScientific Reports2045-23222017-06-017111510.1038/s41598-017-03167-0EV-3, an endogenous human erythropoietin isoform with distinct functional relevanceChristel Bonnas0Liane Wüstefeld1Daniela Winkler2Romy Kronstein-Wiedemann3Ekrem Dere4Katja Specht5Melanie Boxberg6Torsten Tonn7Hannelore Ehrenreich8Herbert Stadler9Inge Sillaber10Epomedics GmbHClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)Clinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)German Red Cross Blood Donor Service North-East, Institute of Transfusion MedicineClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)Institute of Pathology, Technische Universität MünchenInstitute of Pathology, Technische Universität MünchenGerman Red Cross Blood Donor Service North-East, Institute of Transfusion MedicineClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)Epomedics GmbHEpomedics GmbHAbstract Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO.https://doi.org/10.1038/s41598-017-03167-0 |
| spellingShingle | Christel Bonnas Liane Wüstefeld Daniela Winkler Romy Kronstein-Wiedemann Ekrem Dere Katja Specht Melanie Boxberg Torsten Tonn Hannelore Ehrenreich Herbert Stadler Inge Sillaber EV-3, an endogenous human erythropoietin isoform with distinct functional relevance Scientific Reports |
| title | EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_full | EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_fullStr | EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_full_unstemmed | EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_short | EV-3, an endogenous human erythropoietin isoform with distinct functional relevance |
| title_sort | ev 3 an endogenous human erythropoietin isoform with distinct functional relevance |
| url | https://doi.org/10.1038/s41598-017-03167-0 |
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