Ketogenic diet attenuates kainic acid-induced hippocampal cell death by decreasing AMPK/ACC pathway activity and HSP70.
The ketogenic diet (KD) prevents kainic acid (KA)-induced hippocampal cell death. There are reports that AMP-activated protein kinase (AMPK) activation regulates the intracellular signaling pathways involved in cellular survival or apoptotic cell death. In this study, we investigated the effect of the KD consumption on the expression of signaling pathway proteins AMPK and ACC, and heat shock protein (HSP) 70 in mouse hippocampus after KA treatment. Mice were fed the KD for 6 weeks and then sacrificed 48h after KA (30mg/kg) injection. The marked cell death found commonly in normal diet (ND)-fed mice treated with KA was not observed in the KD-fed KA-treated mice. Western blot analysis revealed that phosphorylation of AMPK and ACC was increased after KA treatment. However, phosphorylation of these proteins was reduced in those animals that received the KD. In addition, increased expression of HSP70 in the hippocampus of KA-treated mice was decreased in animals receiving the KD. These results indicate that the KD promotes neuroprotective effects through suppression of the AMPK cascade and that HSP70 is involved in neuronal cell death or oxidative stress.
Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University, School of Medicine, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
Byeong Tak
BT
Jeon
Dong Hoon
DH
Lee
Kyu Hong
KH
Kim
Hyun Joon
HJ
Kim
Sang Soo
SS
Kang
Gyeong Jae
GJ
Cho
Wan Sung
WS
Choi
Gu Seob
GS
Roh
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight; D055423:Diet, Ketogenic; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000633:toxicity; D010766:Phosphorylation; D012640:Seizures / Q000503:physiopathology
D018840:HSP70 Heat-Shock Proteins; D009498:Neurotoxins; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D007608:Kainic Acid