7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways

被引：45

作者：

Ryu, Min Ju ^{[1
]}

Kang, Kyoung Ah ^{[2
,3
]}

Piao, Mei Jing ^{[2
,3
]}

Kim, Ki Cheon ^{[2
,3
]}

Zheng, Jian ^{[2
,3
]}

Yao, Cheng Wen ^{[2
,3
]}

Cha, Ji Won ^{[2
,3
]}

Chung, Ha Sook ^{[1
]}

Kim, Sang Cheol ^{[4
]}

Jung, Eunsun ^{[4
]}

Park, Deokhoon ^{[4
]}

Chae, Sungwook ^{[5
]}

Hyun, Jin Won ^{[2
,3
]}

机构：

[1] Duksung Womens Univ, Seoul 132714, South Korea

[2] Jeju Natl Univ, Sch Med, Cheju 690756, South Korea

[3] Jeju Natl Univ, Inst Nucl Sci & Technol, Cheju 690756, South Korea

[4] Biospectrum Life Sci Inst, Songnam 44213, Gyunggi Do, South Korea

[5] Korea Inst Oriental Med, Aging Res Ctr, Taejon 305811, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2014年 / 33卷 / 04期

关键词：

human keratinocytes; heme oxygenase-1; 7,8-dihydroxyflavone; cytoprotection; oxidative stress; nuclear factor erythroid 2-related factor 2; HEME OXYGENASE-1; GENE-EXPRESSION; MOLECULAR-MECHANISMS; PC12; CELLS; ACTIVATION; NRF2; ELEMENT; FLAVONOIDS; INRF2; PHOSPHORYLATION;

D O I：

10.3892/ijmm.2014.1643

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

This study investigated the effect of 7,8-dihydroxyflavone (DHF) on the expression and activity of heme oxygenase-1 (HO-1), an enzyme with potent antioxidant properties, as well as the molecular mechanisms involved. DHF markedly upregulated HO-1 mRNA and protein expression in human keratinocytes (HaCaT cells), resulting in increased HO-1 activity. DHF also increased the protein level of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates HO-1 expression by binding to the antioxidant response element (ARE) within the HO-1 gene promoter, in a time-dependent manner. Moreover, DHF decreased the expression of Kelch-like ECH-associated protein 1, a repressor of Nrf2 activity, and induced the translocation of Nrf2 from the cytosol into the nucleus, thereby allowing its association with the ARE site. DHF activated extracellular-regulated kinase (ERK) and protein kinase B (PKB, Akt) in keratinocytes, while the ERK and Akt inhibitors attenuated DHF-enhanced Nrf2 and HO-1 expression. DHF also protected the keratinocytes against hydrogen peroxide- and ultraviolet B-induced oxidative damage, while HO-1, ERK and Akt inhibitors markedly suppressed DHF-mediated cytoprotection. Taken together, the results suggested that DHF activates ERK- and Akt-Nrf2 signaling cascades in HaCaT cells, leading to the upregulation of HO-1 and cytoprotection against oxidative stress.

引用

页码：964 / 970

页数：7

共 37 条

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