Kaltschmidt B, Baeuerle P A, Kaltschmidt C
Institute for Biochemistry, University of Freiburg, Germany.
Mol Aspects Med. 1993;14(3):171-90. doi: 10.1016/0098-2997(93)90004-w.
Reactive oxygen intermediates (ROIs) are involved in many neurological diseases. Despite the toxic nature of these compounds, low concentrations of ROIs can function as signaling molecules. One target for their signaling function is the inducible transcription factor NF-kappa B. Predominantly in lymphoid cells, induction of NF-kappa B in response to oxidative stress leads to transcriptional activation of many genes which are relevant for pathogen defense. These include the TNF, IL-6, IL-8, GM-CSF, beta-interferon, MHC class I and V-CAM genes. However, NF-kappa B is also abundant in various cell types of the nervous system, including neurons. We propose that NF-kappa B plays a role as a redox-controlled transcriptional activator also in cells of the nervous system and in that property may contribute to neurological disorders. Our finding that some neurons from healthy brain contain constitutively active NF-kappa B suggests a role of NF-kappa B in normal brain function as well.
活性氧中间体(ROIs)与许多神经系统疾病有关。尽管这些化合物具有毒性,但低浓度的ROIs可作为信号分子发挥作用。其信号功能的一个靶点是诱导型转录因子NF-κB。主要在淋巴细胞中,氧化应激诱导NF-κB会导致许多与病原体防御相关的基因转录激活。这些基因包括肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、β-干扰素、MHC I类基因和血管细胞黏附分子(V-CAM)基因。然而,NF-κB在包括神经元在内的神经系统的各种细胞类型中也大量存在。我们提出,NF-κB在神经系统细胞中也作为氧化还原控制的转录激活因子发挥作用,并且这一特性可能导致神经系统疾病。我们发现,来自健康大脑的一些神经元含有组成型活性NF-κB,这也表明NF-κB在正常脑功能中发挥作用。