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Phosphatidylethanolamine-Binding Protein 1 Ameliorates Ischemia-Induced Inflammation and Neuronal Damage in the Rabbit Spinal Cord

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Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea
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Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea
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Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea
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Department of Neurosurgery, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Pyeongchon 14068, Korea
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Department of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 24253, Korea
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Department of Neurosurgery, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 07441, Korea
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Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Korea
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Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong 18450, Korea
9
Research Institute for Complementary & Alternative Medicine, Hallym University, Chuncheon 24253, Korea
*
Authors to whom correspondence should be addressed.
These co-authors equally contributed to this article.
Cells 2019, 8(11), 1370; https://doi.org/10.3390/cells8111370
Received: 5 September 2019 / Revised: 25 October 2019 / Accepted: 29 October 2019 / Published: 31 October 2019
(This article belongs to the Section Cellular Pathology)
In a previous study, we utilized a proteomic approach and found a significant reduction in phosphatidylethanolamine-binding protein 1 (PEBP1) protein level in the spinal cord at 3 h after ischemia. In the present study, we investigated the role of PEBP1 against oxidative stress in NSC34 cells in vitro, and ischemic damage in the rabbit spinal cord in vivo. We generated a PEP-1-PEBP1 fusion protein to facilitate the penetration of blood-brain barrier and intracellular delivery of PEBP1 protein. Treatment with PEP-1-PEBP1 significantly decreased cell death and the induction of oxidative stress in NSC34 cells. Furthermore, administering PEP-1-PEBP1 did not show any significant side effects immediately before and after ischemia/reperfusion. Administration of PEP-PEBP1 improved the Tarlov’s neurological score at 24 and 72 h after ischemia, and significantly improved neuronal survival at 72 h after ischemia based on neuronal nuclei (NeuN) immunohistochemistry, Flouro-Jade B staining, and western blot study for cleaved caspase 3. PEP-1-PEBP1 administration decreased oxidative stress based on malondialdehyde level, advanced oxidation protein products, and 8-iso-prostaglandin F2α in the spinal cord. In addition, inflammation based on myeloperoxidase level, tumor necrosis factor-α level, and high mobility group box 1 level was decreased by PEP-1-PEBP1 treatment at 72 h after ischemia. Thus, PEP-1-PEBP1 treatment, which decreases oxidative stress, inflammatory cytokines, and neuronal death, may be an effective therapeutic strategy for spinal cord ischemia. View Full-Text
Keywords: phosphatidylethanolamine-binding protein 1; ischemia; oxidative stress; inflammation; spinal cord phosphatidylethanolamine-binding protein 1; ischemia; oxidative stress; inflammation; spinal cord
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Kim, W.; Cho, S.B.; Jung, H.Y.; Yoo, D.Y.; Oh, J.K.; Choi, G.-M.; Cho, T.-G.; Kim, D.W.; Hwang, I.K.; Choi, S.Y.; Moon, S.M. Phosphatidylethanolamine-Binding Protein 1 Ameliorates Ischemia-Induced Inflammation and Neuronal Damage in the Rabbit Spinal Cord. Cells 2019, 8, 1370.

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