title: Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways.
abstract: Recently, we demonstrated that myricetin exhibits cytoprotective effects against H(2)O(2)-induced cell damage via its antioxidant properties. In the present study, myricetin was found to inhibit H(2)O(2)-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic bodies, nuclear fragmentation, sub-G(1) cell population, and disruption of mitochondrial membrane potential (Δψ(m)), which are increased in H(2)O(2)-treated cells. Western blot data showed that in H(2)O(2)-treated cells, myricetin increased the level of Bcl-2, which is an anti-apoptotic factor, and decreased the levels of Bax, active caspase-9 and -3, which are pro-apoptotic factors. And myricetin inhibited release of cytochrome c from mitochondria to cytosol in H(2)O(2)-treated cells. Myricetin-induced survival correlated with Akt activity, and the rescue of cells by myricetin treatment against H(2)O(2)-induced apoptosis was inhibited by the specific PI3K (phosphoinositol-3-kinase) inhibitor. Myricetin-mediated survival also inhibited the activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which are members of MAPK. Our studies suggest that myricetin prevents oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways.
authors.affiliation: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju 690-756, Korea; E-Mails: legna48@hanmail.net (K.A.K); wzh407@hotmail.com (Z.H.W); zhangrui26@hotmail.com (R.Z); mjpiao@hanmail.net (M.J.P); svv771@hanmail.net (K.C.K).
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D005419:Flavonoids; C040015:myricetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt