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6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats
Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563815/ https://www.ncbi.nlm.nih.gov/pubmed/32841050 http://dx.doi.org/10.1177/0963689720950226 |
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author | Gao, Liansheng Wang, Chun Qin, Bing Li, Tao Xu, Weilin Lenahan, Cameron Ying, Guangyu Li, Jianru Zhao, Tengfei Zhu, Yongjian Chen, Gao |
author_facet | Gao, Liansheng Wang, Chun Qin, Bing Li, Tao Xu, Weilin Lenahan, Cameron Ying, Guangyu Li, Jianru Zhao, Tengfei Zhu, Yongjian Chen, Gao |
author_sort | Gao, Liansheng |
collection | PubMed |
description | Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprotective role of PFKFB3 in t-SCI. A compressive clip was introduced to establish the t-SCI model. Herein, we identified that PFKFB3 was extensively distributed in neurons, and PFKFB3 levels significantly increased and peaked 24 h after t-SCI. Additionally, knockdown of PFKFB3 inhibited glycolysis, accompanied by aggravated neuronal apoptosis and white matter injury, while pharmacological activation of PFKFB3 with meclizine significantly enhanced glycolysis, attenuated t-SCI-induced spinal cord injury, and alleviated neurological impairment. The PFKFB3 agonist, meclizine, activated cyclin-dependent kinase 1 (CDK1) and promoted the phosphorylation of p27, ultimately suppressing neuronal apoptosis. However, the neuroprotective effects of meclizine against t-SCI were abolished by the CDK1 antagonist, RO3306. In summary, our data demonstrated that PFKFB3 contributes robust neuroprotection against t-SCI by enhancing glycolysis and modulating CDK1-related antiapoptotic signals. Moreover, targeting PFKFB3 may be a novel and promising therapeutic strategy for t-SCI. |
format | Online Article Text |
id | pubmed-7563815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-75638152020-10-26 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats Gao, Liansheng Wang, Chun Qin, Bing Li, Tao Xu, Weilin Lenahan, Cameron Ying, Guangyu Li, Jianru Zhao, Tengfei Zhu, Yongjian Chen, Gao Cell Transplant Original Article Apoptosis is a vital pathological factor that accounts for the poor prognosis of traumatic spinal cord injury (t-SCI). The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is a critical regulator for energy metabolism and proven to have antiapoptotic effects. This study aimed to investigate the neuroprotective role of PFKFB3 in t-SCI. A compressive clip was introduced to establish the t-SCI model. Herein, we identified that PFKFB3 was extensively distributed in neurons, and PFKFB3 levels significantly increased and peaked 24 h after t-SCI. Additionally, knockdown of PFKFB3 inhibited glycolysis, accompanied by aggravated neuronal apoptosis and white matter injury, while pharmacological activation of PFKFB3 with meclizine significantly enhanced glycolysis, attenuated t-SCI-induced spinal cord injury, and alleviated neurological impairment. The PFKFB3 agonist, meclizine, activated cyclin-dependent kinase 1 (CDK1) and promoted the phosphorylation of p27, ultimately suppressing neuronal apoptosis. However, the neuroprotective effects of meclizine against t-SCI were abolished by the CDK1 antagonist, RO3306. In summary, our data demonstrated that PFKFB3 contributes robust neuroprotection against t-SCI by enhancing glycolysis and modulating CDK1-related antiapoptotic signals. Moreover, targeting PFKFB3 may be a novel and promising therapeutic strategy for t-SCI. SAGE Publications 2020-08-25 /pmc/articles/PMC7563815/ /pubmed/32841050 http://dx.doi.org/10.1177/0963689720950226 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Gao, Liansheng Wang, Chun Qin, Bing Li, Tao Xu, Weilin Lenahan, Cameron Ying, Guangyu Li, Jianru Zhao, Tengfei Zhu, Yongjian Chen, Gao 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase 1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in Rats |
title | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses
Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase
1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in
Rats |
title_full | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses
Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase
1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in
Rats |
title_fullStr | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses
Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase
1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in
Rats |
title_full_unstemmed | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses
Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase
1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in
Rats |
title_short | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Suppresses
Neuronal Apoptosis by Increasing Glycolysis and “cyclin-dependent kinase
1-Mediated Phosphorylation of p27 After Traumatic Spinal Cord Injury in
Rats |
title_sort | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase suppresses
neuronal apoptosis by increasing glycolysis and “cyclin-dependent kinase
1-mediated phosphorylation of p27 after traumatic spinal cord injury in
rats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563815/ https://www.ncbi.nlm.nih.gov/pubmed/32841050 http://dx.doi.org/10.1177/0963689720950226 |
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