Ceruloplasmin is an endogenous protectant against kainate neurotoxicity
Autor: | Sung Youl Lee, Hyoung-Chun Kim, Myung-Bok Wie, The-Vinh Tran, Chun Kee Chung, Eun-Joo Shin, Yoon Hee Chung, Ji Hoon Jeong, Wei-Yi Ong, Hwa-Jung Kim, Eon Sub Park, Dae-Joong Kim, Yunsung Nam |
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Rok vydání: | 2015 |
Předmět: |
Adult
Male medicine.medical_specialty Adolescent Protein oxidation medicine.disease_cause Biochemistry Neuroprotection Lipid peroxidation Rats Sprague-Dawley chemistry.chemical_compound Young Adult Physiology (medical) Internal medicine medicine Animals Humans CA1 Region Hippocampal chemistry.chemical_classification Reactive oxygen species Epilepsy Kainic Acid biology Hydroxyl Radical Neurotoxicity Ceruloplasmin Glutathione Middle Aged medicine.disease Oxidative Stress Endocrinology chemistry Case-Control Studies biology.protein Female Lipid Peroxidation Oxidative stress |
Zdroj: | Free radical biologymedicine. 84 |
ISSN: | 1873-4596 |
Popis: | 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. |
Databáze: | OpenAIRE |
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