Phosphoglycerate mutase 1 reduces neuronal damage in the hippocampus following ischemia/reperfusion through the facilitation of energy utilization

Woosuk Kim; Hyun Jung Kwon; Hyo Young Jung; Dae Young Yoo; Dae Won Kim; In Koo Hwang

doi:10.1016/j.neuint.2019.104631

Phosphoglycerate mutase 1 reduces neuronal damage in the hippocampus following ischemia/reperfusion through the facilitation of energy utilization

Neurochem Int. 2020 Feb:133:104631. doi: 10.1016/j.neuint.2019.104631. Epub 2019 Dec 10.

Authors

Woosuk Kim¹, Hyun Jung Kwon², Hyo Young Jung³, Dae Young Yoo⁴, Dae Won Kim⁵, In Koo Hwang⁶

Affiliations

¹ Department of Biomedical Sciences, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea; 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 Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
⁴ Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan, 31151, South Korea.
⁵ Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea. Electronic address: kimdw@gwnu.ac.kr.
⁶ Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea. Electronic address: vetmed2@snu.ac.kr.

PMID: 31836547
DOI: 10.1016/j.neuint.2019.104631

Abstract

In a previous study, we observed the effect of phosphoglycerate mutase 1 (PGAM1) on proliferating cells and neuroblasts in the subgranular zone of mouse dentate gyrus. In the present study, we examined the roles of PGAM1 in the HT22 hippocampal cell line and in gerbil hippocampus after H₂O₂-induced oxidative stress and after ischemia/reperfusion, respectively. Control-PGAM1 and Tat-PGAM1 proteins were synthesized using Tat-1 expression vector since Tat-1 fusion proteins can easily cross the blood-brain barrier and cell membranes. We found that transduction of Tat-PGAM1 protein into HT22 cells was dose- and time-dependent. Delivery of the protein to the cytoplasm was confirmed by western blotting and immunocytochemistry. Treatment of HT22 cells with Tat-PGAM1 protein showed a concentration-dependent reduction in cell damage and decreased formation of reactive oxygen species after H₂O₂ exposure. Tat-PGAM1 administration significantly ameliorated the ischemia-induced hyperactivity in gerbils at 1 day after ischemia/reperfusion. Additionally, a pronounced decrease in neuronal damage and reactive gliosis were observed in the hippocampal CA1 region of the Tat-PGAM1-treated group at 4 days after ischemia/reperfusion compared to that in the vehicle (Tat peptide) or control-PGAM1-treated groups. Administration of Tat-PGAM1 mitigated the changes in ATP content, succinate dehydrogenase activity, pH, and 4-hydroxynonenal levels in the hippocampus at 4 and 7 days after ischemia/reperfusion compared to that in the vehicle-treated group. In addition, administration of Tat-PGAM1 significantly ameliorated the ischemia-induced increases of lactate levels in the hippocampus at 15 min and 6 h after ischemia/reperfusion than in the vehicle or control-PGAM1-treated groups. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to prevent neuronal damage from oxidative stress or ischemia.

Keywords: Energy production; Gerbil; Ischemia; Oxidative stress; Phosphoglycerate mutase 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Brain Ischemia / chemically induced
Brain Ischemia / metabolism
Cell Survival / drug effects
Gerbillinae
Hippocampus / drug effects
Hippocampus / metabolism*
Hippocampus / pathology
Hydrogen Peroxide / pharmacology
Ischemia / chemically induced
Ischemia / metabolism
Male
Neurons / metabolism*
Neuroprotective Agents / pharmacology
Oxidative Stress / drug effects*
Phosphoglycerate Mutase / metabolism*
Reactive Oxygen Species / metabolism*
Reperfusion / methods

Substances

Neuroprotective Agents
Reactive Oxygen Species
Hydrogen Peroxide
Phosphoglycerate Mutase