7,8-Dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways
7,8-Dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways
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7,8-二羟基黄酮通过调节 PI3K/Akt 和 JNK 通路保护 PC12 细胞免受 6-羟基多巴胺诱导的细胞死亡
DOI：
10.1016/j.neulet.2014.08.016
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发表时间：
2014-10-03
影响因子：
2.5
通讯作者：
Qu, Zhi-Qiang
中科院分区：
文献类型：
--
作者：
Han, Xiao-Hua;Cheng, Meng-Nan;Qu, Zhi-Qiang
We have recently shown that 7,8-dihydroxyflavone (7,8-DHF) protects PC12 cells against 6-OHDA-induced cytotoxicity through its antioxidant activity. In the present study, we investigated the molecular mechanisms underlying the neuronal protective activity of 7,8-DHF. Western blot analysis showed that 6-OHDA (100 mu M, 24 h) enhanced the phosphorylation of JNK and ERK1/2, but it markedly suppressed the expression of p-Akt, implying that 6-OHDA induces PC12 cell death through activating the proapoptotic MAPKs pathway but suppressing the survival PI3K/Akt pathway. More importantly, addition of 7,8-DHF fully prevented the activation of JNK and suppression of Akt induced by 6-OHDA. Interestingly, pretreatment with the PI3K-specific inhibitor LY294002 largely blocked 7,8-DHF function in protecting PC12 cells from 6-OHDA-induced cell death. In contrast, the MEK inhibitor PD98059 showed little effect on the protective activity of 7,8-DHF. These results suggest that 7,8-DHF might protect PC12 cells from 6-OHDA-induced cell death through activating PI3K/Akt pathway and inhibiting JNK pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
