Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression.

doi:10.1021/jf904061x

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/25159

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Title:	Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression.
Authors:	CHIA-WEI LIN MING-JIUAN WU INGRID Y.-C. LIU JENG-DIAN SU JUI-HUNG YEN
Contributors:	生物科技系
Keywords:	Luteolin PC12 cells HO-1 Nrf2 ARE ERK
Date:	2010-04
Issue Date:	2012-03-30 15:17:50 (UTC+8)
Publisher:	Amer Chemical Soc
Abstract:	Luteolin (3′,4′,5,7-tetrahydroxyflavone), a food-derived flavonoid, has been reported to possess antioxidant, anti-inflammatory, and anticancer activities. In this work, we assessed whether luteolin has neurotrophic activity, namely, the ability to induce neurite outgrowth and to attenuate serum withdrawal-induced cytotoxicity in PC12 cells. Our results show that luteolin significantly induced neurite outgrowth along with increased expression of the differentiation marker, growth-associated protein-43 (GAP-43), in PC12 cells dose-dependently. Incubation of serum-deprived PC12 cells with luteolin prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1) mRNA and protein levels, and enhanced the binding of nuclear factor E2-related factor 2 (Nrf2) to antioxidant response element (ARE), which works as an enhancer sequence in the HO-1 promoter. Addition of zinc protoporphyrin (Znpp), a selective HO-1 competitive inhibitor, significantly reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1. Luteolin also persistently activated extracellular signal-regulated protein kinase 1/2 (ERK1/2); while the addition of U0126, a pharmacological MEK/ERK inhibitor, attenuated luteolin-induced Nrf2 binding activity, HO-1 expression, cytoprotective effect, and neurite outgrowth. Taken together, the above findings suggest that luteolin induces neurite outgrowth and augments cellular antioxidant defense capacity, at least in part, through the activation of the ERK signaling pathway.
Relation:	Journal of Agricultural and Food Chemistry 58(7)：p.4477-4489
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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