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Ceruloplasmin is an endogenous protectant against kainate neurotoxicity

Title
Ceruloplasmin is an endogenous protectant against kainate neurotoxicity
Authors
Shin, Eun-JooJeong, Ji HoonChung, Chun KeeKim, Dae-JoongWie, Myung-BokPark, Eon SubChung, Yoon HeeNam, YunsungThe-Vinh TranLee, Sung YoulKim, Hwa-JungOng, Wei-YiKim, Hyoung-Chun
Ewha Authors
김화정
SCOPUS Author ID
김화정scopus
Issue Date
2015
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN
0891-5849JCR Link1873-4596JCR Link
Citation
vol. 84, pp. 355 - 372
Keywords
CeruloplasminKainateOxidative stressIronFerritinClutathioneEpileptic patientsHippocampusGliaFree radicals
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
To determine the role of ceruloplasmin (Cp) in epileptic seizures, we used a kainate (KA) seizure animal model and examined hippocampal samples from epileptic patients. Treatment with KA resulted in a time-dependent decrease in Cp protein expression in the hippocampus of rats. Cp-positive cells were colocalized with neurons or reactive astrocytes in KA-treated rats and epileptic patient samples. KA-induced seizures, initial oxidative stress (i.e., hydroxyl radical formation, lipid peroxidation, protein oxidation, and synaptosomal reactive oxygen species), altered iron status (increasing Fe2+ accumulation and L-ferritin-positive reactive microglial cells and decreasing H-ferritin-positive neurons), and impaired glutathione homeostasis and neurodegeneration (i.e., Fluoro-Nissl and Fluoro-Jade B staining analyses) were more pronounced in Cp antisense oligonucleotide (ASO)- than in Cp sense oligonucleotide-treated rats. Consistently, Cp ASO facilitated KA-induced lactate dehydrogenase (LDH) release, Fe2+ accumulation, and glutathione loss in neuron-rich and mixed cultures. However, Cp ASO did not alter KA-induced LDH release or Fe2+ accumulation in the astroglial culture, but did facilitate impairment in glutathione homeostasis in the same culture. Importantly, treatment with human Cp protein resulted in a significant attenuation against these neurotoxicities induced by Cp ASO. Our results suggest that Cp-mediated neuroprotection occurs via the inhibition of seizure-associated oxidative damage (including impairment in glutathione homeostasis), Fe2+ accumulation, and alterations in ferritin immunoreactivity. Moreover, interactive modulation between neurons and glia was found to be important for Cp upregulation in the attenuation of epileptic damage in both animals and humans. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2015.03.031
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약학대학 > 약학과 > Journal papers
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