Ketogenic diet protects the hippocampus from kainic acid toxicity by inhibiting the dissociation of bad from 14-3-3.
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.
Noh
Hae Sook
HS
Department of Anatomy and Neurobiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University, Jinju, Gyeongnam, South Korea.
Kim
Yoon Sook
YS
Kim
Young Hee
YH
Han
Jae Yoon
JY
Park
Chang Hwan
CH
Kang
Ahn Ki
AK
Shin
Hee Suk
HS
Kang
Sang Soo
SS
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D050528:Diet, Carbohydrate-Restricted / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D047468:Immunoprecipitation / Q000379:methods; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051025:bcl-Associated Death Protein / Q000378:metabolism*
D048948:14-3-3 Proteins; D051025:bcl-Associated Death Protein; D053148:Caspase 3; D007608:Kainic Acid