Ceruloplasmin is an endogenous protectant against kainate neurotoxicity.


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 Fe(2+) 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, Fe(2+) accumulation, and glutathione loss in neuron-rich and mixed cultures. However, Cp ASO did not alter KA-induced LDH release or Fe(2+) 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), Fe(2+) 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.

DOI: 10.1016/j.freeradbiomed.2015.03.031
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@article{Shin2015CeruloplasminIA, title={Ceruloplasmin is an endogenous protectant against kainate neurotoxicity.}, author={Eun-joo Shin and Ji Hoon Jeong and Chun Kee Chung and Dae-joong Kim and Myung-Bok Wie and Eon Sub Park and Yoon Hee Chung and Yunsung Nam and The-Vinh Tran and Sung Youl Lee and Hwa-Jung Kim and Wei-Yi Ong and Hyoung Chun Kim}, journal={Free radical biology & medicine}, year={2015}, volume={84}, pages={355-372} }