Luteolin Modulates 6-Hydroxydopamine-Induced Transcriptional Changes of Stress Response Pathways in PC12 Cells

doi:10.1371/journal.pone.0097880

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Title:	Luteolin Modulates 6-Hydroxydopamine-Induced Transcriptional Changes of Stress Response Pathways in PC12 Cells
Authors:	Hu, Ling-Wei Yen, Jui-Hung Shen, Yi-Ting Wu, Kuan-Yi Wu, Ming-Jiuan
Contributors:	生物科技系藥學系
Keywords:	ENDOPLASMIC-RETICULUM STRESS UNFOLDED PROTEIN RESPONSE HEME OXYGENASE-1 EXPRESSION NERVE GROWTH-FACTOR OXIDATIVE STRESS PARKINSONS-DISEASE ER STRESS DNA-DAMAGE LIPID-PEROXIDATION GENE-EXPRESSION
Date:	2014-05
Issue Date:	2015-05-06 21:22:40 (UTC+8)
Publisher:	Public Library Science
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 mu M) 30 min prior to 6-OHDA (100 mu M) 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, GADD45 alpha and PUMA, were reduced by luteolin. Luteolin also significantly down-regulated 6-OHDA-mediated unfolded protein response (UPR), leading to decreases in phospho-eIF2 alpha, 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.
Relation:	Plos One, v.9 n.5, e97880
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles [Dept. of Biotechnology (including master's program)] Periodical Articles

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