Ketogenic diet protects the hippocampus from kainic acid toxicity by inhibiting the dissociation of bad from 14-3-3
✍ Scribed by Hae Sook Noh; Yoon Sook Kim; Young Hee Kim; Jae Yoon Han; Chang Hwan Park; Ahn Ki Kang; Hee Suk Shin; Sang Soo Kang; Gyeong Jae Cho; Wan Sung Choi
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 415 KB
- Volume
- 84
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
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.