Djavaheri-Mergny M, Gras M P, Mergny J L, Dubertret L
Laboratoire de Dermatologie, INSERM U312, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris, France.
Biochem J. 1999 Mar 15;338 ( Pt 3)(Pt 3):607-13.
Previous reports have demonstrated an increase in nuclear factor-kappaB (NF-kappaB) activity in response to UV radiation. These studies have essentially focused on the DNA-damaging fraction of solar UV radiation (UV-B and UV-C). In contrast, the effects of UV-A radiation (320-400 nm) on NF-kappaB are not well known. In this study, we present evidence that UV-A radiation induces a marked decrease in NF-kappaB DNA-binding activity in NCTC 2544 human keratinocytes. In addition, NCTC 2544 keratinocytes pretreated with UV-A fail to respond to NF-kappaB inducers. Moreover, UV-A radiation induces a decrease in NF-kappaB-driven luciferase reporter gene expression in NCTC 2544 keratinocytes. The expression of the gene encoding IkappaBalpha (IkappaB is the NF-kappaB inhibitor), which is closely associated with NF-kappaB activity, is also reduced (3-fold) upon UV-A treatment. Our results indicate that the UV-A-induced decrease in NF-kappaB DNA-binding activity is associated with a decrease in the levels of the p50 and p65 protein subunits. This is the first evidence that an oxidative stress, such as UV-A radiation, may induce a specific decrease in NF-kappaB activity in mammalian cells, probably through degradation of NF-kappaB protein subunits. These findings suggest that UV-A could modulate the NF-kappaB-dependent gene expression.
先前的报告表明，核因子-κB（NF-κB）活性会因紫外线辐射而增加。这些研究主要集中在太阳紫外线辐射（UV-B和UV-C）的DNA损伤部分。相比之下，UV-A辐射（320 - 400纳米）对NF-κB的影响尚不清楚。在本研究中，我们提供证据表明，UV-A辐射会导致NCTC 2544人角质形成细胞中NF-κB的DNA结合活性显著降低。此外，经UV-A预处理的NCTC 2544角质形成细胞对NF-κB诱导剂无反应。而且，UV-A辐射会使NCTC 2544角质形成细胞中NF-κB驱动的荧光素酶报告基因表达降低。与NF-κB活性密切相关的编码IκBα（IκB是NF-κB抑制剂）的基因表达在UV-A处理后也降低了（3倍）。我们的结果表明，UV-A诱导的NF-κB DNA结合活性降低与p50和p65蛋白亚基水平的降低有关。这是首个证据表明，诸如UV-A辐射这样的氧化应激可能会导致哺乳动物细胞中NF-κB活性特异性降低，可能是通过NF-κB蛋白亚基的降解。这些发现表明，UV-A可能会调节NF-κB依赖的基因表达。
