title: 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways.
abstract: 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.
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China. Electronic address: xiaohua.han@163.com.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Han
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Meng-Nan
authors.initials: MN
authors.lastname: Cheng
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Qingdao University Medical College, Qingdao, China.
authors.forename: Xue-Ting
authors.initials: XT
authors.lastname: Li
authors.affiliation: Central Laboratory, the Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Qu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D002867:Chromones; D047309:Flavones; D005419:Flavonoids; D009025:Morpholines; D018696:Neuroprotective Agents; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C485383:6,7-dihydroxyflavone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: 6-Hydroxydopamine; 7,8-Dihydroxyflavone; Akt; JNK; PC12 cells