NADPH oxidase and cyclooxygenase mediate the ultraviolet B-induced generation of reactive oxygen species and activation of nuclear factor-κB in HaCaT human keratinocytes
NADPH oxidase and cyclooxygenase mediate the ultraviolet B-induced generation of reactive oxygen species and activation of nuclear factor-κB in HaCaT human keratinocytes
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DOI：
10.1016/j.biochi.2004.06.010
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发表时间：
2004-07-01
期刊：
影响因子：
3.9
通讯作者：
Kim, JA
中科院分区：
文献类型：
--
作者：
Beak, SM;Lee, YS;Kim, JA
紫外线B（UVB）照射的有害影响与UVB增强活性氧（ROS）的产生有关。然而，UVB产生的ROS的确切来源尚未明确揭示。在这项研究中，我们确定了ROS产生的来源及其在UVB诱导的HaCaT人角质形成细胞核因子（NF）-κ B活化中的作用。UVB照射产生的活性氧在剂量依赖性的方式，这是显着抑制二苯碘鎓（DPI），夹竹桃素（Apo）和新蝶呤（Neo），抑制剂的NADPH氧化酶，吲哚美辛（Indo），环氧合酶（考克斯）抑制剂，但不被线粒体电子传递抑制剂和其他胞质酶抑制剂。此外，这些NADPH氧化酶和考克斯抑制剂显著阻断UVB辐射诱导的NF-κ B核转位。这些结果表明，NADPH氧化酶和考克斯可能是UVB诱导的活性氧产生的主要来源，并在NF-kappaB的激活中发挥重要作用，NF-kappaB参与UVB诱导HaCaT细胞中多种基因的表达。这些结果进一步表明，这些酶可能是UVB诱导的皮肤损伤的预防策略的良好目标。(C)2004年，Elsevier SAS。All rights reserved.
The detrimental effects of ultraviolet B (UVB) irradiation have been connected with the enhanced generation of reactive oxygen species (ROS) by UVB. However, the exact source of ROS produced by UVB has not been clearly revealed yet. In this study, we determined the source of ROS production and its role in the UVB-induced activation of nuclear factor (NF)-kappaB in HaCaT human keratinocytes. UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors. In addition, these inhibitors of the NADPH oxidase and COX significantly blocked the UVB irradiation-induced nuclear translocation of NF-kappaB. These results suggest that the NADPH oxidase and COX may be major sources for the UVB-induced ROS generation, and play an essential role in the activation of NF-kappaB which is involved in the expression of a variety of genes induced by UVB in HaCaT cells. These results further suggest that these enzymes may be good targets for the preventive strategy of UVB-induced skin injury. (C) 2004 Elsevier SAS. All rights reserved.