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The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein
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The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein
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Journal Article
The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein
2015
Overview
Both genetic and environmental factors are important in the pathogenesis of Parkinson＇s disease. As α-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson＇s disease, genetic aspects of α-synuclein is widely studied. However, the influence of dietary factors such as quercetin on α-synuclein was rarely studied. Herein we aimed to study the neuroprotective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin on α-synuclein expression. PC12 cells were pre-treated with quercetin（100, 500, 1,000 μM） and then together with various drugs such as 1-methyl-4-phenylpyridinium（MPP＋; a free radical generator）, 6-hydroxydopamine（6-OHDA; a free radical generator）, ammonium chloride（an autophagy inhibitor）, and nocodazole（an aggresome inhibitor）. Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide（MTT） assay. Apoptosis was detected by annexin V-fluorescein isothiocyanate and propidium iodide through the use of fluorescence activated cell sorter. α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking out α-synuclein using RNA interference. Cell viability increased at lower concentrations（100 and 500 μM） of quercetin but decreased at higher concentration（1,000 μM）. Quercetin exerted neuroprotective effect against MPP＋, ammonium chloride and nocodazole at 100 μM. MPP＋ induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment increased α-synuclein expression. However, knocking out α-synuclein exerted no significant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agents via affecting various mechanisms such as apoptosis, autophagy and aggresome. Because α-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson＇s disease pathogenesis needs further investigation.
Publisher
Medknow Publications & Media Pvt. Ltd,Department of Neurology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea%Department of Neurology, College of Medicine, Seoul National University, Seoul, Republic of Korea,Medknow Publications & Media Pvt Ltd,Wolters Kluwer Medknow Publications
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