Myricetin attenuated MPP +-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells

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-apopt...

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Veröffentlicht in:Neuropharmacology 2011-07, Vol.61 (1), p.329-335
Hauptverfasser: Zhang, Kai, Ma, ZeGang, Wang, Jun, Xie, AnMu, Xie, JunXia
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container_title Neuropharmacology
container_volume 61
creator Zhang, Kai
Ma, ZeGang
Wang, Jun
Xie, AnMu
Xie, JunXia
description 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. The neuroprotective function of myricetin may be mediated by an inhibition of both oxidative stress and MKK4 activation. [Display omitted] ► Myricetin protects MES23.5 cells from MPP +-induced cell death. ► Myricetin inhibits MPP +-induced oxidative stress and mitochondria dysfunction. ► Myricetin suppresses the MKK4 and JNK activity. ► Myricetin reverses the MPP +-induced Bcl/Bax system dysfunction.
doi_str_mv 10.1016/j.neuropharm.2011.04.021
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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. The neuroprotective function of myricetin may be mediated by an inhibition of both oxidative stress and MKK4 activation. [Display omitted] ► Myricetin protects MES23.5 cells from MPP +-induced cell death. ► Myricetin inhibits MPP +-induced oxidative stress and mitochondria dysfunction. ► Myricetin suppresses the MKK4 and JNK activity. ► Myricetin reverses the MPP +-induced Bcl/Bax system dysfunction.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/j.neuropharm.2011.04.021</identifier><identifier>PMID: 21549720</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>1-Methyl-4-phenylpyridinium - toxicity ; Antioxidants - pharmacology ; Cells, Cultured ; Enzyme Activation - drug effects ; Enzyme Activation - physiology ; Flavonoids - pharmacology ; Humans ; JNK Mitogen-Activated Protein Kinases - antagonists &amp; inhibitors ; JNK Mitogen-Activated Protein Kinases - metabolism ; MAP Kinase Kinase 4 - antagonists &amp; inhibitors ; MAP Kinase Kinase 4 - metabolism ; Membrane Potential, Mitochondrial - drug effects ; Membrane Potential, Mitochondrial - physiology ; MKK4 ; MPP ; Myricetin ; Oxidative stress ; Protein Kinase Inhibitors - pharmacology</subject><ispartof>Neuropharmacology, 2011-07, Vol.61 (1), p.329-335</ispartof><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. 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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. The neuroprotective function of myricetin may be mediated by an inhibition of both oxidative stress and MKK4 activation. [Display omitted] ► Myricetin protects MES23.5 cells from MPP +-induced cell death. ► Myricetin inhibits MPP +-induced oxidative stress and mitochondria dysfunction. ► Myricetin suppresses the MKK4 and JNK activity. ► Myricetin reverses the MPP +-induced Bcl/Bax system dysfunction.</description><subject>1-Methyl-4-phenylpyridinium - toxicity</subject><subject>Antioxidants - pharmacology</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - physiology</subject><subject>Flavonoids - pharmacology</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists &amp; inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>MAP Kinase Kinase 4 - antagonists &amp; inhibitors</subject><subject>MAP Kinase Kinase 4 - metabolism</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Membrane Potential, Mitochondrial - physiology</subject><subject>MKK4</subject><subject>MPP</subject><subject>Myricetin</subject><subject>Oxidative stress</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EokPhFZB3LFDCtXOT2Euoyt90oBKwthzbUT2aiQfbqYjEw-PpFFh2dXWs7_hc-xBCGdQMWPdmW09ujuFwo-O-5sBYDVgDZ4_Iiom-qXro8DFZAXBRNRLEGXmW0hYAUDDxlJxx1qLsOazI780SvXHZT1Tn7KZZZ2fp5vqavq78ZGdTlFlyyOGXNz4vdFionrKvirY6-1B8k6V-uvGDv5NhpJv1Gu-OP39ZU22yvz2RJWRz-Y03dUuN2-3Sc_Jk1LvkXtzPc_Lj_eX3i4_V1dcPny7eXlUGoc2VG8o7RiubrkWQLXfYAcNR2jKxbaQeWy4dHxAHNHLkVuKgYeiNsdwBds05eXW69xDDz9mlrPY-HTfQkwtzUqJHJrhA_jDZybYT2LJCihNpYkgpulEdot_ruCgG6liS2qr_JaljSQpQlZKK9eV9yDzsnf1n_NtKAd6dAFc-5da7qJLxbipd-OhMVjb4h1P-AOIbp4w</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Zhang, Kai</creator><creator>Ma, ZeGang</creator><creator>Wang, Jun</creator><creator>Xie, AnMu</creator><creator>Xie, JunXia</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20110701</creationdate><title>Myricetin attenuated MPP +-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells</title><author>Zhang, Kai ; 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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. The neuroprotective function of myricetin may be mediated by an inhibition of both oxidative stress and MKK4 activation. [Display omitted] ► Myricetin protects MES23.5 cells from MPP +-induced cell death. ► Myricetin inhibits MPP +-induced oxidative stress and mitochondria dysfunction. ► Myricetin suppresses the MKK4 and JNK activity. ► Myricetin reverses the MPP +-induced Bcl/Bax system dysfunction.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>21549720</pmid><doi>10.1016/j.neuropharm.2011.04.021</doi><tpages>7</tpages></addata></record>
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subjects 1-Methyl-4-phenylpyridinium - toxicity
Antioxidants - pharmacology
Cells, Cultured
Enzyme Activation - drug effects
Enzyme Activation - physiology
Flavonoids - pharmacology
Humans
JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases - metabolism
MAP Kinase Kinase 4 - antagonists & inhibitors
MAP Kinase Kinase 4 - metabolism
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - physiology
MKK4
MPP
Myricetin
Oxidative stress
Protein Kinase Inhibitors - pharmacology
title Myricetin attenuated MPP +-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells
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