Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase
Abstract Cytokine receptor-like factor 3 (CRLF3) is a conserved but largely uncharacterized orphan cytokine receptor of eumetazoan animals. CRLF3-mediated neuroprotection in insects can be stimulated with human erythropoietin. To identify mechanisms of CRLF3-mediated neuroprotection we studied the e...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22035-0 |
| _version_ | 1797984632567758848 |
|---|---|
| author | Debbra Y. Knorr Kristin Schneider Luca Büschgens Jan Förster Nadine S. Georges Bart R. H. Geurten Ralf Heinrich |
| author_facet | Debbra Y. Knorr Kristin Schneider Luca Büschgens Jan Förster Nadine S. Georges Bart R. H. Geurten Ralf Heinrich |
| author_sort | Debbra Y. Knorr |
| collection | DOAJ |
| description | Abstract Cytokine receptor-like factor 3 (CRLF3) is a conserved but largely uncharacterized orphan cytokine receptor of eumetazoan animals. CRLF3-mediated neuroprotection in insects can be stimulated with human erythropoietin. To identify mechanisms of CRLF3-mediated neuroprotection we studied the expression and proapoptotic function of acetylcholinesterase in insect neurons. We exposed primary brain neurons from Tribolium castaneum to apoptogenic stimuli and dsRNA to interfere with acetylcholinesterase gene expression and compared survival and acetylcholinesterase expression in the presence or absence of the CRLF3 ligand erythropoietin. Hypoxia increased apoptotic cell death and expression of both acetylcholinesterase-coding genes ace-1 and ace-2. Both ace genes give rise to single transcripts in normal and apoptogenic conditions. Pharmacological inhibition of acetylcholinesterases and RNAi-mediated knockdown of either ace-1 or ace-2 expression prevented hypoxia-induced apoptosis. Activation of CRLF3 with protective concentrations of erythropoietin prevented the increased expression of acetylcholinesterase with larger impact on ace-1 than on ace-2. In contrast, high concentrations of erythropoietin that cause neuronal death induced ace-1 expression and hence promoted apoptosis. Our study confirms the general proapoptotic function of AChE, assigns a role of both ace-1 and ace-2 in the regulation of apoptotic death and identifies the erythropoietin/CRLF3-mediated prevention of enhanced acetylcholinesterase expression under apoptogenic conditions as neuroprotective mechanism. |
| first_indexed | 2024-04-11T07:04:46Z |
| format | Article |
| id | doaj.art-b46bf4caefa44ab498c36ac1b9f1668a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T07:04:46Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b46bf4caefa44ab498c36ac1b9f1668a2022-12-22T04:38:25ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-22035-0Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesteraseDebbra Y. Knorr0Kristin Schneider1Luca Büschgens2Jan Förster3Nadine S. Georges4Bart R. H. Geurten5Ralf Heinrich6Department of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenDepartment of Cellular Neurobiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-University GöttingenAbstract Cytokine receptor-like factor 3 (CRLF3) is a conserved but largely uncharacterized orphan cytokine receptor of eumetazoan animals. CRLF3-mediated neuroprotection in insects can be stimulated with human erythropoietin. To identify mechanisms of CRLF3-mediated neuroprotection we studied the expression and proapoptotic function of acetylcholinesterase in insect neurons. We exposed primary brain neurons from Tribolium castaneum to apoptogenic stimuli and dsRNA to interfere with acetylcholinesterase gene expression and compared survival and acetylcholinesterase expression in the presence or absence of the CRLF3 ligand erythropoietin. Hypoxia increased apoptotic cell death and expression of both acetylcholinesterase-coding genes ace-1 and ace-2. Both ace genes give rise to single transcripts in normal and apoptogenic conditions. Pharmacological inhibition of acetylcholinesterases and RNAi-mediated knockdown of either ace-1 or ace-2 expression prevented hypoxia-induced apoptosis. Activation of CRLF3 with protective concentrations of erythropoietin prevented the increased expression of acetylcholinesterase with larger impact on ace-1 than on ace-2. In contrast, high concentrations of erythropoietin that cause neuronal death induced ace-1 expression and hence promoted apoptosis. Our study confirms the general proapoptotic function of AChE, assigns a role of both ace-1 and ace-2 in the regulation of apoptotic death and identifies the erythropoietin/CRLF3-mediated prevention of enhanced acetylcholinesterase expression under apoptogenic conditions as neuroprotective mechanism.https://doi.org/10.1038/s41598-022-22035-0 |
| spellingShingle | Debbra Y. Knorr Kristin Schneider Luca Büschgens Jan Förster Nadine S. Georges Bart R. H. Geurten Ralf Heinrich Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase Scientific Reports |
| title | Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase |
| title_full | Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase |
| title_fullStr | Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase |
| title_full_unstemmed | Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase |
| title_short | Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase |
| title_sort | protection of insect neurons by erythropoietin crlf3 mediated regulation of pro apoptotic acetylcholinesterase |
| url | https://doi.org/10.1038/s41598-022-22035-0 |
| work_keys_str_mv | AT debbrayknorr protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT kristinschneider protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT lucabuschgens protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT janforster protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT nadinesgeorges protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT bartrhgeurten protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase AT ralfheinrich protectionofinsectneuronsbyerythropoietincrlf3mediatedregulationofproapoptoticacetylcholinesterase |