Ahn Tae-Beom, Jeon Beom S
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 ; Department of Neurology, Movement Disorder Center, Parkinson Study Group, and Neuroscience Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Neural Regen Res. 2015 Jul;10(7):1113-9. doi: 10.4103/1673-5374.160106.
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.
遗传因素和环境因素在帕金森病的发病机制中都很重要。由于α-突触核蛋白是路易小体的主要成分，而路易小体是帕金森病的病理标志，因此对α-突触核蛋白的遗传方面进行了广泛研究。然而，槲皮素等饮食因素对α-突触核蛋白的影响却鲜有研究。在此，我们旨在研究槲皮素对影响细胞凋亡、自噬和聚集体的各种毒素的神经保护作用，以及槲皮素对α-突触核蛋白表达的作用。PC12细胞先用槲皮素（100、500、1000μM）预处理，然后再与各种药物共同处理，如1-甲基-4-苯基吡啶离子（MPP(+)；一种自由基生成剂）、6-羟基多巴胺（6-OHDA；一种自由基生成剂）、氯化铵（一种自噬抑制剂）和诺考达唑（一种聚集体抑制剂）。使用3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）法测定细胞活力。通过膜联蛋白V-异硫氰酸荧光素和碘化丙啶，利用荧光激活细胞分选仪检测细胞凋亡。通过蛋白质免疫印迹法和免疫组织化学法检测α-突触核蛋白的表达。利用RNA干扰敲除α-突触核蛋白，进一步研究其作用。较低浓度（100和500μM）的槲皮素可提高细胞活力，但较高浓度（1000μM）时则降低细胞活力。100μM的槲皮素对MPP(+)、氯化铵和诺考达唑具有神经保护作用。100μM的槲皮素可降低MPP(+)诱导的细胞凋亡。槲皮素处理可增加α-突触核蛋白的表达。然而，敲除α-突触核蛋白对细胞存活无显著影响。总之，槲皮素通过影响细胞凋亡、自噬和聚集体等多种机制对毒性药物具有神经保护作用。由于槲皮素可增加α-突触核蛋白的表达，其作为环境因素在帕金森病发病机制中的作用需要进一步研究。
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