7,8-Dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways

• Published in: Neuroscience letters 2014-10, Vol.581, p.85-88
• Main Authors: Han, Xiao-Hua, Cheng, Meng-Nan, Chen, Lei, Fang, Hui, Wang, Li-Juan, Li, Xue-Ting, Qu, Zhi-Qiang
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; 7,8-Dihydroxyflavone; Akt; Animals; Apoptosis - drug effects; Cell Survival - drug effects; Chromones - pharmacology; Flavones - pharmacology; Flavonoids - pharmacology; JNK; MAP Kinase Signaling System; Morpholines - pharmacology; Neuroprotective Agents - pharmacology; Oxidopamine - toxicity; PC12 Cells; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Rats
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2014.08.016

•7,8-DHF protects PC12 cells from 6-OHDA-induced cell death.•6-OHDA activates the pro-apoptotic MAPK pathways but inhibits the anti-apoptotic PI3K/Akt pathways.•The protective effect of 7,8-DHF might be mediated by modulating PI3K/Akt and JNK pathways. 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 (100μM, 24h) 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 pro-apoptotic 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.