title: Ketogenic diet protects the hippocampus from kainic acid toxicity by inhibiting the dissociation of bad from 14-3-3.
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.
authors.affiliation: Department of Anatomy and Neurobiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University, Jinju, Gyeongnam, South Korea.
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Noh
authors.forename: Yoon Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Han
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Park
authors.forename: Ahn Ki
authors.initials: AK
authors.lastname: Kang
authors.forename: Hee Suk
authors.initials: HS
authors.lastname: Shin
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
mesh_terms: 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*
chemical_list: D048948:14-3-3 Proteins; D051025:bcl-Associated Death Protein; D053148:Caspase 3; D007608:Kainic Acid