Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord.

Abstract

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.

• Authors: Hyo Young Jung, Hyun Jung Kwon, Woosuk Kim, Kyu Ri Hahn, Seung Myung Moon, Yeo Sung Yoon, Dae Won Kim, In Koo Hwang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 19 (Oct 08 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33050051 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Neuroprotective Agents
• tat Gene Products, Human Immunodeficiency Virus
• Hydrogen Peroxide
• Phosphoglycerate Mutase

Topics

• Animals
• Cell Death (drug effects)
• Cytokines (metabolism)
• Disease Models, Animal
• Drug Delivery Systems (methods)
• Hybrid Cells
• Hydrogen Peroxide (pharmacology)
• Male
• Mice
• Motor Neurons (drug effects, metabolism)
• Myelitis (drug therapy)
• Neuroprotective Agents (administration & dosage)
• Oxidative Stress (drug effects)
• Phosphoglycerate Mutase (administration & dosage)
• Rabbits
• Signal Transduction (drug effects)
• Spinal Cord Ischemia (drug therapy)
• tat Gene Products, Human Immunodeficiency Virus (chemistry)