1. Luteolin Modulates 6-Hydroxydopamine-Induced Transcriptional Changes of Stress Response Pathways in PC12 Cells.
- Author
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Hu, Ling-Wei, Yen, Jui-Hung, Shen, Yi-Ting, Wu, Kuan-Yi, and Wu, Ming-Jiuan
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LUTEOLIN , *6-Hydroxydopamine , *GENETIC transcription , *PHYSIOLOGICAL stress , *NEUROTOXIC agents , *OXIDATIVE stress , *PARKINSON'S disease - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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