Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation
Brain-derived neurotrophic factor (BDNF) has robust effects on synaptogenesis, neuronal differentiation and synaptic transmission and plasticity. The maturation of BDNF is a complex process. Proprotein convertase 1/3 (PC1/3) has a key role in the cleavage of protein precursors that are directed to r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1066;epage=1070;aulast=Zhang |
| _version_ | 1811333819317354496 |
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| author | Xiang-Yang Zhang Feng Liu Yan Chen Wei-Chun Guo Zhao-Hui Zhang |
| author_facet | Xiang-Yang Zhang Feng Liu Yan Chen Wei-Chun Guo Zhao-Hui Zhang |
| author_sort | Xiang-Yang Zhang |
| collection | DOAJ |
| description | Brain-derived neurotrophic factor (BDNF) has robust effects on synaptogenesis, neuronal differentiation and synaptic transmission and plasticity. The maturation of BDNF is a complex process. Proprotein convertase 1/3 (PC1/3) has a key role in the cleavage of protein precursors that are directed to regulated secretory pathways; however, it is not clear whether PC1/3 mediates the change in BDNF levels caused by ischemia. To clarify the role of PC1/3 in BDNF maturation in ischemic cortical neurons, primary cortical neurons from fetal rats were cultured in a humidified environment of 95% N2 and 5% CO2 in a glucose-free Dulbecco’s modified Eagle’s medium at 37°C for 3 hours. Enzyme-linked immunosorbent assays and western blotting showed that after oxygen-glucose deprivation, the secreted and intracellular levels of BDNF were significantly reduced and the intracellular level of PC1/3 was decreased. Transient transfection of cortical neurons with a PC1/3 overexpression plasmid followed by oxygen-glucose deprivation resulted in increased PC1/3 levels and increased BDNF levels. When levels of the BDNF precursor protein were reduced, the concentration of BDNF in the culture medium was increased. These results indicate that PC1/3 cleavage of BDNF is critical for the conversion of pro-BDNF in rat cortical neurons during ischemia. The study was approved by the Animal Ethics Committee of Wuhan University School of Basic Medical Sciences. |
| first_indexed | 2024-04-13T16:58:33Z |
| format | Article |
| id | doaj.art-3b6cf984e5a34adbb9af286c5bf8641e |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-13T16:58:33Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-3b6cf984e5a34adbb9af286c5bf8641e2022-12-22T02:38:44ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-011561066107010.4103/1673-5374.270314Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivationXiang-Yang ZhangFeng LiuYan ChenWei-Chun GuoZhao-Hui ZhangBrain-derived neurotrophic factor (BDNF) has robust effects on synaptogenesis, neuronal differentiation and synaptic transmission and plasticity. The maturation of BDNF is a complex process. Proprotein convertase 1/3 (PC1/3) has a key role in the cleavage of protein precursors that are directed to regulated secretory pathways; however, it is not clear whether PC1/3 mediates the change in BDNF levels caused by ischemia. To clarify the role of PC1/3 in BDNF maturation in ischemic cortical neurons, primary cortical neurons from fetal rats were cultured in a humidified environment of 95% N2 and 5% CO2 in a glucose-free Dulbecco’s modified Eagle’s medium at 37°C for 3 hours. Enzyme-linked immunosorbent assays and western blotting showed that after oxygen-glucose deprivation, the secreted and intracellular levels of BDNF were significantly reduced and the intracellular level of PC1/3 was decreased. Transient transfection of cortical neurons with a PC1/3 overexpression plasmid followed by oxygen-glucose deprivation resulted in increased PC1/3 levels and increased BDNF levels. When levels of the BDNF precursor protein were reduced, the concentration of BDNF in the culture medium was increased. These results indicate that PC1/3 cleavage of BDNF is critical for the conversion of pro-BDNF in rat cortical neurons during ischemia. The study was approved by the Animal Ethics Committee of Wuhan University School of Basic Medical Sciences.http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1066;epage=1070;aulast=Zhangcortical neuron; ischemia; neurotrophin; oxygen-glucose deprivation; precursor protein of brain-derived neurotrophic factor; proprotein convertase; proprotein convertase 1/3 |
| spellingShingle | Xiang-Yang Zhang Feng Liu Yan Chen Wei-Chun Guo Zhao-Hui Zhang Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation Neural Regeneration Research cortical neuron; ischemia; neurotrophin; oxygen-glucose deprivation; precursor protein of brain-derived neurotrophic factor; proprotein convertase; proprotein convertase 1/3 |
| title | Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation |
| title_full | Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation |
| title_fullStr | Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation |
| title_full_unstemmed | Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation |
| title_short | Proprotein convertase 1/3-mediated down-regulation of brain-derived neurotrophic factor in cortical neurons induced by oxygen-glucose deprivation |
| title_sort | proprotein convertase 1 3 mediated down regulation of brain derived neurotrophic factor in cortical neurons induced by oxygen glucose deprivation |
| topic | cortical neuron; ischemia; neurotrophin; oxygen-glucose deprivation; precursor protein of brain-derived neurotrophic factor; proprotein convertase; proprotein convertase 1/3 |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=6;spage=1066;epage=1070;aulast=Zhang |
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