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Kwon, Hyug Moo
Immunometabolism and Cancer Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorder, Genomic instability

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Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappa B-mediated neuroinflammation in kainic acid-induced seizures

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Title
Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappa B-mediated neuroinflammation in kainic acid-induced seizures
Author
Shin, H.J.Kim, H.Heo, R.W.Kim, H.J.Choi, W.S.Kwon, H. MooRoh, G.S.
Issue Date
2014-07
Publisher
NATURE PUBLISHING GROUP
Citation
CELL DEATH AND DIFFERENTIATION, v.21, no.7, pp.1095 - 1106
Abstract
Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood-brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote (+/-) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP (+/-) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP (+/-) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-κB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target.
URI
https://scholarworks.unist.ac.kr/handle/201301/4074
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84902291471
DOI
10.1038/cdd.2014.29
ISSN
1350-9047
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BIO_Journal Papers
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