Research Paper Volume 14, Issue 22 pp 8886—8899

Phosphoglycerate kinase 1 protects against ischemic damage in the gerbil hippocampus

Kyu Ri Hahn1, *, , Hyun Jung Kwon2,3, *, , Yeo Sung Yoon1, , Dae Won Kim2, , In Koo Hwang1, ,

  • 1 Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea
  • 2 Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, South Korea
  • 3 Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
* Equal contribution

Received: January 6, 2022       Accepted: October 10, 2022       Published: October 18, 2022
How to Cite

Copyright: © 2022 Hahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Phosphoglycerate kinase 1 (PGK1) is a metabolic enzyme that converts 1,3-diphosphoglycerate to 3-phosphoglycerate. In the current study, we synthesized a PEP-1-PGK1 fusion protein that can cross the blood-brain barrier and cell membrane, and the effects of PEP-1-PGK1 against oxidative stress were investigated HT22 cells and ischemic gerbil brain. The PEP-1-PGK1 protein and its control protein (Con-PGK1) were treated and permeability was evaluated HT22 cells. The PEP-1-PGK1 was introduced into HT22 cells depending on its concentration and incubation time and was gradually degraded over 36 h after treatment. PEP-1-PGK1, but not Con-PGK1, significantly ameliorated H2O2-induced cell damage and reactive oxygen species formation in HT22 cells. Additionally, PEP-1-PGK1, but not Con-PGK1, mitigated ischemia-induced hyperlocomotion 1 d after ischemia and 4 d after ischemia of neuronic cell death. PEP-1-PGK1 treatment significantly alleviated the raised lactate and succinate dehydrogenase activities in the early (15 min to 6 h) and late (4 and 7 d) stages of ischemia, respectively. In addition, PEP-1-PGK1 treatment ameliorated the decrease in ATP and pH levels in the late stage (2–7 d) of ischemia. Nuclear factor erythroid-2-related factor 2 (Nrf2) levels accelerated the ischemia-induced increase in the hippocampus 1 d after ischemia after PEP-1-PGK1 treatment. Neuroprotective and ameliorative effects were prominent at a low concentration (0.1 mg/kg), but not at a high concentration (1 mg/kg), of PEP-1-PGK1. Collectively, low concentrations of PEP-1-PGK1 prevented neuronal stress by increasing energy production.


PGK1: phosphoglycerate kinase 1; ROS: reactive oxygen species; PFKFB3: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3; PGAM1: phosphoglycerate mutase 1; MPP: 1-methyl-4-phenylpyridinium; Nrf2: nuclear factor erythroid-2-related factor 2; Con-PGK1: control PGK1; ELISA: enzyme-linked immunosorbent assay; 5-CFDA AM: 5-carboxyfluorescein diacetate acetoxymethyl ester; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; DCF-DA: 2,7-dichlorofluorescein diacetate; NeuN: neuronal nuclei; GFAP: glial fibrillary acidic protein; Iba-1: ionized calcium-binding adapter molecule 1; MDA: malondialdehyde; DCF: dichlorofluorescein.