Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line
Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line
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DOI：
10.1016/s0891-5849(98)00212-3
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发表时间：
1999-01-01
影响因子：
7.4
通讯作者：
Packer, L
中科院分区：
文献类型：
--
作者：
Saliou, C;Kitazawa, M;Packer, L
人体皮肤暴露于紫外线 (UVR) 下会导致皮肤抗氧化剂的消耗、基因表达的调节，并最终导致皮肤病的发生。尽管外源补充抗氧化剂可以防止紫外线诱导的光氧化损伤，但它们对导致基因表达的细胞信号通路成分的影响尚未明确。在本研究中，研究了抗氧化剂 α-硫辛酸、N-乙酰基-L-半胱氨酸 (NAC) 和类黄酮提取物水飞蓟素在暴露于太阳紫外线模拟器后调节 HaCaT 角质形成细胞中转录因子核因子 kappa B (NF-kappa B) 和激活蛋白 1 (AP-1) 激活的能力。 NF-kappa B 和 AP-1 的激活显示出相似的时间模式：在紫外线照射后 2 小时检测到激活，并维持长达 8 小时。为了确定激活的 NF-κ B 刺激转录的能力，使用报告基因测定法测量 NF-κ B 依赖性基因表达。暴露后 3 小时评估抗氧化剂对 NF-κ B 和 AP-1 激活的影响。高浓度的 NAC 可以实现完全抑制，而低浓度的 α-硫辛酸和水飞蓟素则可以显着抑制 NF-κ B 的激活。相比之下，AP-1 的激活仅被 NAC 部分抑制，而 α-硫辛酸或水飞蓟素则完全不抑制。这些结果表明，α-硫辛酸和水飞蓟素等抗氧化剂可以通过对 NF-κ B 激活的选择性作用，有效调节细胞对 WR 的反应。 (C) 1998 爱思唯尔科学公司。
Exposure of the human skin to ultraviolet radiation (UVR) leads to depletion of cutaneous antioxidants, regulation of gene expression and ultimately to the development of skin diseases. Although exogenous supplementation of antioxidants prevents UVR-induced photooxidative damage, their effects on components of cell signalling pathways leading to gene expression has not been clearly established. In the present study, the effects of the antioxidants alpha-lipoic acid, N-acetyl-L-cysteine (NAC) and the flavonoid extract silymarin were investigated for their ability to modulate the activation of the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) in HaCaT keratinocytes after exposure to a solar UV simulator. The activation of NF-kappa B and AP-1 showed a similar temporal pattern: activation was detected 2 h after UV exposure and maintained for up to 8 hr. To determine the capacity of activated NF-kappa B to stimulate transcription, NF-kappa B-dependent gene expression was measured using a reporter gene assay. The effects of the antioxidants on NF-kappa B and AP-1 activation were evaluated 3 h after exposure. While a high concentration of NAC could achieve a complete inhibition, low concentrations of alpha-lipoic acid and silymarin were shown to significantly inhibit NF-kappa B activation. In contrast AP-1 activation was only partially inhibited by NAC, and not at all by alpha-lipoic acid or silymarin. These results indicate that antioxidants such as alpha-lipoic acid and silymarin can efficiently modulate the cellular response to WR through their selective action on NF-kappa B activation. (C) 1998 Elsevier Science Inc.