Resveratrol protects human keratinocytes HaCaT cells from UVA-induced oxidative stress damage by downregulating Keap1 expression

Resveratrol protects human keratinocytes HaCaT cells from UVA-induced oxidative stress damage by downregulating Keap1 expression
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白藜芦醇通过下调 Keap1 表达保护人角质形成细胞 HaCaT 细胞免受 UVA 诱导的氧化应激损伤

DOI:
10.1016/j.ejphar.2010.10.009
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发表时间:
2011-01-10
影响因子:
5
通讯作者:
Zhou, Deshan
Zhou, Deshan
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Yong;Chan, Fangxiao;Zhou, Deshan

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紫外线辐射A(UVA)诱导的氧化应激被认为是皮肤癌变的重要因素。白藜芦醇在机体内具有显著的抗氧化活性。本研究旨在探讨白藜芦醇对人角质形成细胞(HaCaT)抗UVA诱导的氧化损伤的保护作用及NF-E2相关因子2(Nrf 2)移位的可能机制。用紫外线照射HaCaT细胞,观察白藜芦醇对细胞活力、活性氧产生和膜脂质过氧化的影响。免疫荧光染色、Western blot和定量PCR分别检测UVA暴露导致细胞活力下降和活性氧增加白藜芦醇能有效地提高UVA照射后HaCaT细胞的存活率,保护其免受UVA诱导的氧化应激。白藜芦醇还能增加Nrf 2蛋白的水平,促进Nrf 2在细胞核中的积累,从而上调抗氧化酶的活性。处理12小时及以后,尽管Keap 1 mRNA的水平仍然增加,但我们的结果表明,白藜芦醇可以降解Keap 1蛋白并促进Nrf 2在细胞核中的积累,从而保护HaCaT细胞免受UVA诱导的氧化应激白藜芦醇可能是一种更有用的天然药物,用于保护表皮细胞免受UVA诱导的损伤(C)2010 Elsevier B V保留所有权利
Ultraviolet radiation A (UVA)-induced oxidative stress is recognized as an important factor in the development of skin carcinogenesis Resveratrol is demonstrated to possess remarkable antioxidant activity in the organism The aim of this study was to investigate the protective role of resveratrol in human keratinocytes (HaCaT) against UVA induced oxidative damage and the possible mechanism of the translocation of NF-E2-related factor-2 (Nrf2) into the nucleus The HaCaT cells were UVA-Irradiated and the effects of resveratrol on cell viability reactive oxygen species generation and membrane lipid peroxidation were measured The proteins and mRNA of Nrf2 and Kelch-like-ECH-associated protein 1 (Keap1) were determined by immunofluorescence staining Western blot and quantitative PCR respectively UVA exposure led to a decrease in viability and an Increase in reactive oxygen species generation in HaCaT cells Resveratrol could effectively increase the viability of HaCaT cells after UVA exposure and protect them from UVA induced oxidative stress Moreover resveratrol increased the level of Nrf2 protein and facilitated Nrf2 accumulation in the nucleus as a result the activity of antioxidant enzymes was also upregulated The main finding was that Keap1 protein a repressor of Nrf2 in the cytoplasm was clearly decreased by resveratrol treatment 12 h and beyond though the level of Keap1 mRNA still increased Our results suggest that resveratrol can degrade Keap1 protein and facilitate Nrf2 accumulation in the nucleus thereby protecting HaCaT cells from UVA-Induced oxidative stress Resveratrol could be a more useful natural medicine for the protection of epidermal cells from UVA-induced damage (C) 2010 Elsevier B V All rights reserved