Luteolin modulates 6-hydroxydopamine-induced transcriptional changes of stress response pathways in PC12 cells.
Luteolin modulates 6-hydroxydopamine-induced transcriptional changes of stress response pathways in PC12 cells.
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DOI：
10.1371/journal.pone.0097880
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wu MJ
中科院分区：
文献类型：
--
作者：
Hu LW;Yen JH;Shen YT;Wu KY;Wu MJ
神经毒素6-羟多巴胺（6-OHDA）引起与氧化和蛋白毒性应激相关的转录变化，已被广泛用于生成帕金森病的实验模型。食源性化合物木犀草素具有抗氧化、抗炎和神经营养等多靶点作用。本研究的目的是探讨木犀草素如何影响6-羟色胺介导的应激反应途径。结果表明，在6-OHDA（100µM）处理PC12细胞前30分钟，木犀草素（20µM）预处理PC12细胞，6-OHDA诱导的ROS过量产生、细胞毒性、caspase-3激活和BIM、TRB3和GADD34 mRNA表达显著减弱。此外，木犀草素减少了6- ohda介导的细胞周期阻滞和p53靶基因p21、GADD45α和PUMA的转录。木樨草素还显著下调6- ohda介导的未折叠蛋白反应（UPR），导致磷酸化eif2 α、ATF4、GRP78和CHOP降低。此外，木犀草素可减弱6- ohda诱导的nrf2介导的HO-1和GCLC。综上所述，这些结果表明木犀草素的神经保护作用可能与细胞内ROS形成的减少和p53、UPR和Nrf2-ARE通路的下调有关。
The neurotoxin 6-hydroxydopamine (6-OHDA), which causes transcriptional changes associated with oxidative and proteotoxic stress, has been widely used to generate an experimental model of Parkinson’s disease. The food-derived compound luteolin has multi-target actions including antioxidant, anti-inflammatory and neurotrophic activities. The aim of this study is to investigate how luteolin affects 6-OHDA-mediated stress response pathways. The results showed that when PC12 cells were pre-treated with luteolin (20 µM) 30 min prior to 6-OHDA (100 µM) exposure, 6-OHDA-induced ROS overproduction, cytotoxicity, caspase-3 activation, and mRNA expression of BIM, TRB3 and GADD34 were significantly attenuated. Moreover, 6-OHDA-mediated cell cycle arrest and transcription of p53 target genes, p21, GADD45α and PUMA, were reduced by luteolin. Luteolin also significantly down-regulated 6-OHDA-mediated unfolded protein response (UPR), leading to decreases in phospho-eIF2α, ATF4, GRP78 and CHOP. In addition, luteolin attenuated 6-OHDA-induced Nrf2-mediated HO-1 and GCLC. Taken together, these results suggest that diminishing intracellular ROS formation and down-regulation of p53, UPR and Nrf2-ARE pathways may be involved in the neuroprotective effect of luteolin.
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影响因子：
9.3
作者：
Dirscherl K;Karlstetter M;Ebert S;Kraus D;Hlawatsch J;Walczak Y;Moehle C;Fuchshofer R;Langmann T
通讯作者：
Langmann T
影响因子：
15.1
作者：
Bernstein AI;Garrison SP;Zambetti GP;O'Malley KL
通讯作者：
O'Malley KL
影响因子：
4.8
作者：
Dey, Souvik;Baird, Thomas D.;Wek, Ronald C.
通讯作者：
Wek, Ronald C.
影响因子：
3.7
作者：
Gélinas, S;Bureau, G;Martinoli, MG
通讯作者：
Martinoli, MG
影响因子：
5.3
作者：
Brush, MH;Weiser, DC;Shenolikar, S
通讯作者：
Shenolikar, S