Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease
Identifieur interne : 000338 ( Ncbi/Curation ); précédent : 000337; suivant : 000339Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease
Auteurs : Yuncheng Wu [République populaire de Chine, États-Unis] ; Xinqun Li [États-Unis] ; Julie Zhu [États-Unis] ; Wenjie Xie [États-Unis] ; Weidong Le [États-Unis] ; Zhen Fan [États-Unis] ; Joseph Jankovic [États-Unis] ; Tianhong Pan [États-Unis]Source :
- Neuro-Signals [ 1424-862X ] ; 2011.
Abstract
Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson's disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models.
Url:
DOI: 10.1159/000328516
PubMed: 21778691
PubMed Central: 3699815
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id="aff5">Diana Helis Henry Medical Research Foundation, New Orleans, La., USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Diana Helis Henry Medical Research Foundation, New Orleans, La.</wicri:regionArea><wicri:noRegion>La.</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21778691</idno><idno type="pmc">3699815</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699815</idno><idno type="RBID">PMC:3699815</idno><idno type="doi">10.1159/000328516</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000285</idno><idno type="wicri:Area/Pmc/Curation">000285</idno><idno type="wicri:Area/Pmc/Checkpoint">000121</idno><idno type="wicri:Area/Ncbi/Merge">000338</idno><idno type="wicri:Area/Ncbi/Curation">000338</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease</title><author><name sortKey="Wu, Yuncheng" sort="Wu, Yuncheng" uniqKey="Wu Y" first="Yuncheng" last="Wu">Yuncheng Wu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Department of Neurology, Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine</wicri:regionArea><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Li, Xinqun" sort="Li, Xinqun" uniqKey="Li X" first="Xinqun" last="Li">Xinqun Li</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Tex., USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Tex.</wicri:regionArea><wicri:noRegion>Tex.</wicri:noRegion></affiliation></author><author><name sortKey="Zhu, Julie Xiaohong" sort="Zhu, Julie Xiaohong" uniqKey="Zhu J" first="Julie" last="Zhu">Julie Zhu</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion></affiliation></author><author><name sortKey="Xie, Wenjie" sort="Xie, Wenjie" uniqKey="Xie W" first="Wenjie" last="Xie">Wenjie Xie</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion></affiliation></author><author><name sortKey="Le, Weidong" sort="Le, Weidong" uniqKey="Le W" first="Weidong" last="Le">Weidong Le</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion></affiliation></author><author><name sortKey="Fan, Zhen" sort="Fan, Zhen" uniqKey="Fan Z" first="Zhen" last="Fan">Zhen Fan</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Tex., USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Tex.</wicri:regionArea><wicri:noRegion>Tex.</wicri:noRegion></affiliation></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3">Department of Neurology, Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Center and Movement Disorder Clinic, Baylor College of Medicine</wicri:regionArea><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university">Baylor College of Medicine</orgName><placeName><settlement type="city">Houston</settlement><region type="state">Texas</region></placeName><orgName type="university" n="3">Baylor College of Medicine</orgName></affiliation></author><author><name sortKey="Pan, Tianhong" sort="Pan, Tianhong" uniqKey="Pan T" first="Tianhong" last="Pan">Tianhong Pan</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Neurology, Parkinson's Disease Research Laboratory, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Parkinson's Disease Research Laboratory</wicri:regionArea><wicri:noRegion>Parkinson's Disease Research Laboratory</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Diana Helis Henry Medical Research Foundation, New Orleans, La., USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Diana Helis Henry Medical Research Foundation, New Orleans, La.</wicri:regionArea><wicri:noRegion>La.</wicri:noRegion></affiliation></author></analytic><series><title level="j">Neuro-Signals</title><idno type="ISSN">1424-862X</idno><idno type="e-ISSN">1424-8638</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson's disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kopin, Ij" uniqKey="Kopin I">IJ Kopin</name></author><author><name sortKey="Markey, Sp" uniqKey="Markey S">SP Markey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sherer, Tb" uniqKey="Sherer T">TB Sherer</name></author><author><name sortKey="Betarberbet, R" uniqKey="Betarberbet R">R Betarberbet</name></author><author><name sortKey="Tasta, Cm" uniqKey="Tasta C">CM Tasta</name></author><author><name sortKey="Seo, Bb" uniqKey="Seo B">BB Seo</name></author><author><name sortKey="Richardson, Jr" uniqKey="Richardson J">JR Richardson</name></author><author><name 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uniqKey="Sinclair D">DA Sinclair</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghosh, Hs" uniqKey="Ghosh H">HS Ghosh</name></author><author><name sortKey="Mcburney, M" uniqKey="Mcburney M">M McBurney</name></author><author><name sortKey="Robbins, Pd" uniqKey="Robbins P">PD Robbins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filomeni, G" uniqKey="Filomeni G">G Filomeni</name></author><author><name sortKey="Graziani, I" uniqKey="Graziani I">I Graziani</name></author><author><name sortKey="De Zio, D" uniqKey="De Zio D">D De Zio</name></author><author><name sortKey="Dini, L" uniqKey="Dini L">L Dini</name></author><author><name sortKey="Centonze, D" uniqKey="Centonze D">D Centonze</name></author><author><name sortKey="Rotilio, G" uniqKey="Rotilio G">G Rotilio</name></author><author><name sortKey="Ciriolo, Mr" uniqKey="Ciriolo M">MR 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