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タイトル :Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults
著者 :Okawara, Mitsugu
Katsuki, Hiroshi
Kurimoto, Emi
Shibata, Haruki
Kume, Toshiaki
Akaike, Akinori
刊行年月日 :2007-2-15
収録雑誌名 :Biochemical Pharmacology
巻 :73
号 :4
開始ページ :550
終了ページ :560
要約(Abstract) :Increasing lines of evidence show that resveratrol, a polyphenol compound contained in several dietary products, exhibits cytoprotective actions. Notably, resveratrol activates sirtuin family of NAD-dependent histone deacetylases implicated in regulation of various cellular processes including gene transcription, DNA repair and apoptosis. Here we examined neuroprotective effect of resveratrol on dopaminergic neurons in organotypic midbrain slice culture. Resveratrol and quercetin, another sirtuin-activating polyphenol, prevented the decrease of dopaminergic neurons and the increase of propidium iodide uptake into slices induced by a dopaminergic neurotoxin 1-methyl-4-phenyl pyridinium (MPP+). Resveratrol also provided concentration-dependent neuroprotective effects against sodium azide, a mitochondrial complex IV inhibitor, and thrombin (EC number 3.4.21.5), a microglia-activating agent. Sirtuin inhibitors such as nicotinamide and sirtinol did not attenuate the protective effect of resveratrol against MPP+ cytotoxicity. Instead, we found that resveratrol prevented accumulation of reactive oxygen species, depletion of cellular glutathione, and cellular oxidative damage induced by MPP+, suggesting involvement of antioxidative properties in the neuroprotective action of resveratrol. On the other hand, resveratrol as well as a sirtuin activator NAD inhibited dopaminergic neurotoxicity of a DNA alkylating agent, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Moreover, MNNG-induced increase in acetylation of p53, a representative target of sirtuin deacetylase activity, was suppressed by resveratrol. These results indicate that resveratrol can exert neuroprotective actions in dopaminergic neurons. Either antioxidative activity or sirtuin-activating potential may play an important role in the neuroprotectice actions of resveratrol against different kinds of insults.
URL :http://www.elsevier.com/locate/biochempharm
収録種別 :雑誌掲載論文
ISSN :00062952
出版社(者) :Elsevier Inc
権利(Rights) :© 2006 Elsevier Inc. All rights reserved.
備考 :平成18~19年度科学研究費補助金(基盤研究(C))研究成果報告書 課題番号:18590052『ミクログリアの活性化を介する黒質線条体系ニューロン変性の機序とその防御』pp.88-98に掲載
URI :http://hdl.handle.net/2298/10012
関連 :http://hdl.handle.net/2298/9868
出現コレクション:研究報告書(薬学系)
このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/2298/10012

 

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