The first two authors contributed equally to this work.
Ketogenic diet protects the hippocampus from kainic acid toxicity by inhibiting the dissociation of bad from 14-3-3
Article first published online: 20 OCT 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 84, Issue 8, pages 1829–1836, December 2006
How to Cite
Noh, H. S., Kim, Y. S., Kim, Y. H., Han, J. Y., Park, C. H., Kang, A. K., Shin, H. S., Kang, S. S., Cho, G. J. and Choi, W. S. (2006), Ketogenic diet protects the hippocampus from kainic acid toxicity by inhibiting the dissociation of bad from 14-3-3. J. Neurosci. Res., 84: 1829–1836. doi: 10.1002/jnr.21057
- Issue published online: 15 NOV 2006
- Article first published online: 20 OCT 2006
- Manuscript Accepted: 20 JUL 2006
- Manuscript Revised: 3 JUL 2006
- Manuscript Received: 18 MAY 2006
- Korea Research Foundation. Grant Number: KRF-2004-005-E00061
- Korea Science and Engineering Foundation. Grant Number: R13-2005-012-01001-0
The ketogenic diet (KD) is often effective for intractable epilepsy, but its antiepileptic mechanisms remain largely unknown. Within the cell death/survival pathway, Akt and its downstream protein Bad play an important role in kainic acid (KA)-induced cell death. Therefore, we investigated the effects of a KD on KA-induced changes in the Akt/Bad/14-3-3 signaling pathway by evaluating Akt, Bad, 14-3-3, and cleaved caspase-3 expression levels as well as their relative interactions. Our results showed that a KD did not affect the expression levels of Akt, Bad, Bcl-xL, Bax, and 14-3-3 but increased phospho-Akt [serine 473; p-Akt (Ser473)] and phospho-Bad [serine 136; p-Bad (Ser136)] expression levels as well as decreased cleaved caspase-3 levels following a KA-induced seizure in the hippocampus. Furthermore, we found that a KD increased the protein–protein interaction between 14-3-3 and p-Bad (Ser136), which might be phosphorylated by p-Akt (Ser473), and decreased interaction of Bad and Bcl-xL. These results suggest that a KD might protect, at least partially, the hippocampus from KA-induced cell death via inhibiting the dissociation of Bad from 14-3-3. © 2006 Wiley-Liss, Inc.