Jeon Byeong Tak, Lee Dong Hoon, Kim Kyu Hong, Kim Hyun Joon, Kang Sang Soo, Cho Gyeong Jae, Choi Wan Sung, Roh Gu Seob
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.
Neurosci Lett. 2009 Mar 27;453(1):49-53. doi: 10.1016/j.neulet.2009.01.068. Epub 2009 Jan 31.
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.
生酮饮食（KD）可预防 kainic 酸（KA）诱导的海马细胞死亡。有报道称，AMP 激活的蛋白激酶（AMPK）激活可调节参与细胞存活或凋亡性细胞死亡的细胞内信号通路。在本研究中，我们调查了食用 KD 对 KA 处理后小鼠海马中信号通路蛋白 AMPK 和 ACC 以及热休克蛋白（HSP）70 表达的影响。小鼠食用 KD 6 周，然后在注射 KA（30mg/kg）48 小时后处死。在用 KA 处理的正常饮食（ND）喂养的小鼠中常见的明显细胞死亡在 KD 喂养的 KA 处理小鼠中未观察到。蛋白质印迹分析显示，KA 处理后 AMPK 和 ACC 的磷酸化增加。然而，在接受 KD 的动物中，这些蛋白质的磷酸化减少。此外，接受 KD 的动物中，KA 处理小鼠海马中 HSP70 的表达增加有所降低。这些结果表明，KD 通过抑制 AMPK 级联反应促进神经保护作用，并且 HSP70 参与神经元细胞死亡或氧化应激。
