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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.

Authors
  • Gao, Liansheng1
  • Wang, Chun1
  • Qin, Bing1
  • Li, Tao1
  • Xu, Weilin1
  • Lenahan, Cameron2
  • Ying, Guangyu1
  • Li, Jianru1
  • Zhao, Tengfei3
  • Zhu, Yongjian1
  • Chen, Gao1
  • 1 Department of Neurosurgery, 89681Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. , (China)
  • 2 448838Burrell College of Osteopathic Medicine, Las Cruces, NM, USA.
  • 3 Department of Orthopedics, 89681Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. , (China)
Type
Published Article
Journal
Cell Transplantation
Publisher
SAGE Publications
Publication Date
Jan 01, 2020
Volume
29
Identifiers
DOI: 10.1177/0963689720950226
PMID: 32841050
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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