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Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit
Hyo Young Jung1, Hyun Jung Kwon2, Woosuk Kim1,3
1Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.
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.
Insights
Tat-PGAM1 fusion protein protects neurons from oxidative stress and spinal cord ischemia. It reduces neuronal death, inflammation, and improves neurological function, suggesting therapeutic potential for neurodegenerative conditions.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Phosphoglycerate mutase 1 (PGAM1) is a key glycolytic enzyme regulating energy metabolism in the brain.
- Oxidative stress and ischemic damage are critical factors in motor neuron degeneration.
Purpose of the Study:
- To investigate the neuroprotective effects of Tat-PGAM1 fusion protein against oxidative stress and spinal cord ischemia.
- To evaluate the efficacy of Tat-PGAM1 in reducing neuronal damage and inflammation.
Main Methods:
- Utilized motor neuron-like (NSC34) cells and a rabbit spinal cord ischemia model.
- Administered Tat-PGAM1 fusion protein, designed for blood-brain barrier penetration.
- Assessed cell viability, oxidative stress markers, inflammatory cytokine levels, and neurological function.
Main Results:
- Tat-PGAM1 effectively entered NSC34 cells and protected them from H2O2-induced oxidative stress and apoptosis.
- In spinal cord ischemia, Tat-PGAM1 treatment significantly improved neurological function and reduced neuronal death.
- Tat-PGAM1 mitigated ischemia-induced oxidative stress markers (malondialdehyde, 8-iso-prostaglandin F2α) and suppressed microglial activation and pro-inflammatory cytokine release (IL-1β, IL-6, TNF-α).
Conclusions:
- Tat-PGAM1 demonstrates significant neuroprotective effects against oxidative stress and spinal cord ischemia.
- The therapeutic potential of Tat-PGAM1 lies in its ability to reduce oxidative stress, neuroinflammation, and neuronal apoptosis.
- Tat-PGAM1 represents a promising therapeutic agent for managing spinal cord injury and related neurodegenerative conditions.
