Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-κB signaling in human epidermal keratinocytes
Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-κB signaling in human epidermal keratinocytes
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DOI：
10.1016/j.freeradbiomed.2005.12.032
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发表时间：
2006-05-01
影响因子：
7.4
通讯作者：
Katiyar, Santosh K.
中科院分区：
文献类型：
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作者：
Mantena, Sudheer K.;Katiyar, Santosh K.
太阳紫外线(UV)辐射引起的氧化应激与多种皮肤病有关。在这里，我们报道了葡萄籽原花青素(GSPs)对紫外线诱导的氧化应激和丝裂原激活蛋白激酶(MAPK)和核因子-kappa B信号通路(NHEK)的光保护作用。用GSP处理NHEK可抑制UVB诱导的过氧化氢(H_2O_2)、脂质过氧化、蛋白质氧化和DNA损伤，并在无细胞体系中清除羟基自由基和超氧阴离子。GSPS还可以抑制UVB诱导的抗氧化防御成分的枯竭。如谷胱甘肽过氧化物酶、过氧化氢酶、超氧化物歧化酶和谷胱甘肽。由于紫外线诱导的氧化应激介导了MAPK和NF-kappa B信号通路的激活，我们确定了GSPs对这些信号通路的影响。在研究的不同时间点，用GSPs处理NHEK可抑制UVB诱导的MAPK家族ERK1/2、JNK和p38蛋白的磷酸化。由于紫外线诱导的H_2O_2在MAPK蛋白的激活中起主要作用，因此用H_2O_2加或不加GSP和其他已知的抗氧化剂处理NHEK。(-)-表没食子儿茶素没食子酸酯、水飞蓟素、抗坏血酸和N-乙酰半胱氨酸。观察到这些抗氧化剂可降低过氧化氢诱导的ERK1/2、JNK和p38的磷酸化。在相同条件下，GSPs还可抑制UVB诱导的NF-kappa B/p65的活化，这一作用分别通过抑制I-kappa Bα和ikkα的降解和激活而实现。综上所述，这些结果表明，GSP在减轻紫外线辐射诱导的人体皮肤氧化应激介导的皮肤病方面是有用的。(C)2006 Elsevier Inc.保留所有权利。
Solar ultraviolet (UV) radiation-induced oxidative stress has been implicated in various skin diseases. Here, we report the photoprotective effect of grape seed proanthocyanidins (GSPs) on UV-induced oxidative stress and activation of mitogen-activated protein kinase (MAPK) and NF-kappa B signaling pathways using normal human epidermal keratinocytes (NHEK). Treatment of NHEK with GSPs inhibited UVB-induced hydrogen peroxide (H2O2), lipid peroxidation, protein oxidation, and DNA damage in NHEK and scavenged hydroxyl radicals and superoxide anions in a cell-free system. GSPs also inhibited UVB-induced depletion of antioxidant defense components,. such as glutathione peroxidase, catalase, superoxide dismutase, and glutathione. As UV-induced oxidative stress mediates activation of MAPK and NF-kappa B signaling pathways, we determined the effects of GSPs on these pathways. Treatment of NHEK with GSPs inhibited UVB-induced phosphorylation of ERK1/2, JNK, and p38 proteins of the MAPK family at the various time points studied. As UV-induced H2O2 plays a major role in activation of MAPK proteins, NHEK were treated with H2O2 with or without GSPs and other known antioxidants, viz. (-)-epigallocatechin-3 -gallate, silymarin, ascorbic acid, and N-acetylcysteine. It was observed that H2O2,induced phosphorylation of ERK1/2, JNK, and p38 was decreased by these antioxidants. Under identical conditions, GSPs also inhibited UVB-induced activation of NF-kappa B/p65, which was mediated through inhibition of degradation and activation Of I kappa B alpha and IKK alpha, respectively. Together, these results Suggest that GSPs could be useful in the attenuation of UV-radiation-induced oxidative stress-mediated skin diseases in human skin. (c) 2006 Elsevier Inc. All rights reserved.