title: Myricetin attenuated MPP(+)-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells.
abstract: Increasing evidence suggests that oxidative stress may be implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD), and anti-oxidation have been shown to be effective to PD treatment. Myricetin has been reported to have the biological functions of anti-oxidation, anti-apoptosis, anti-inflammation and iron-chelation. The aim of the present study is to investigate the neuroprotective effect of myricetin on 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells and the underlying mechanisms. The results showed that myricetin treatment significantly attenuated MPP(+)-induced cell loss and nuclear condensation. Further experiments demonstrated that myricetin could suppress the production of intracellular reactive oxygen species (ROS), restore the mitochondrial transmembrane potential (▵Ψm), increase Bcl-2/Bax ratio and decrease caspase-3 activation that induced by MPP(+). Futhermore, we also showed myricetin decreased the phosphorylation of mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) and c-Jun N-terminal kinase (JNK) caused by MPP(+). These results suggest that myricetin protected the MPP(+)-treated MES23.5 cells by anti-oxidation and inhibition of MKK4 and JNK activation.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao 266071, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Zegang
authors.initials: Z
authors.lastname: Ma
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Anmu
authors.initials: A
authors.lastname: Xie
authors.forename: Junxia
authors.initials: J
authors.lastname: Xie
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; C040015:myricetin; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human; D015655:1-Methyl-4-phenylpyridinium