2. Academic Validation
  3. Git1-PGK1 interaction achieves self-protection against spinal cord ischemia-reperfusion injury by modulating Keap1/Nrf2 signaling

Git1-PGK1 interaction achieves self-protection against spinal cord ischemia-reperfusion injury by modulating Keap1/Nrf2 signaling

  • Redox Biol. 2023 Jun:62:102682. doi: 10.1016/j.redox.2023.102682.
Tao Xu 1,  Peng Gao 2,  Yifan Huang 2,  Mengyuan Wu 2,  Jiang Yi 2,  Zheng Zhou 3,  Xuan Zhao 2,  Tao Jiang 2,  Hao Liu 2,  Tao Qin 2,  Zhenqi Yang 2,  Xiaowei Wang 2,  Tianyi Bao 2,  Jian Chen 4,  Shujie Zhao 5,  Guoyong Yin 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing, 210008, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China.
  • 3 Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
  • 5 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
  • 6 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
PMID: 36963288 DOI: 10.1016/j.redox.2023.102682
Abstract

Spinal cord ischemia-reperfusion (IR) injury (SCIRI) is a significant secondary injury that causes damage to spinal cord neurons, leading to the impairment of spinal cord sensory and motor functions. Excessive Reactive Oxygen Species (ROS) production is considered one critical mechanism of neuron damage in SCIRI. Nonetheless, the molecular mechanisms underlying the resistance of neurons to ROS remain elusive. Our study revealed that the deletion of Git1 in mice led to poor recovery of spinal cord motor function after SCIRI. Furthermore, we discovered that Git1 has a beneficial effect on neuron resistance to ROS production. Mechanistically, Git1 interacted with PGK1, regulated PGK1 phosphorylation at S203, and affected the intermediate products of glycolysis in neurons. The influence of Git1 on glycolysis regulates the dimerization of Keap1, which leads to changes in Nrf2 ubiquitination and plays a role in resisting ROS. Collectively, we show that Git1 regulates the Keap1/Nrf2 axis to resist ROS in a PGK1-dependent manner and thus is a potential therapeutic target for SCIRI.

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