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

1
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
2
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Korea
3
Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea
4
Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong 18450, Korea
5
Research Institute for Complementary & Alternative Medicine, Hallym University, Chuncheon 24253, Korea
*
Authors to whom correspondence should be addressed.
These authors are contributed equally to this article.
Int. J. Mol. Sci. 2020, 21(19), 7425; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197425
Received: 25 August 2020 / Revised: 29 September 2020 / Accepted: 1 October 2020 / Published: 8 October 2020
(This article belongs to the Section Molecular Neurobiology)
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. View Full-Text
Keywords: phosphoglycerate mutase 1; ischemia; spinal cord; oxidative stress; pro-inflammatory cytokine phosphoglycerate mutase 1; ischemia; spinal cord; oxidative stress; pro-inflammatory cytokine
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MDPI and ACS Style

Jung, H.Y.; Kwon, H.J.; Kim, W.; Hahn, K.R.; Moon, S.M.; Yoon, Y.S.; Kim, D.W.; Hwang, I.K. Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord. Int. J. Mol. Sci. 2020, 21, 7425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197425

AMA Style

Jung HY, Kwon HJ, Kim W, Hahn KR, Moon SM, Yoon YS, Kim DW, Hwang IK. Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord. International Journal of Molecular Sciences. 2020; 21(19):7425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197425

Chicago/Turabian Style

Jung, Hyo Y., Hyun J. Kwon, Woosuk Kim, Kyu R. Hahn, Seung M. Moon, Yeo S. Yoon, Dae W. Kim, and In K. Hwang 2020. "Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord" International Journal of Molecular Sciences 21, no. 19: 7425. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197425

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