Department of Experimental Medicine, University of Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy.
Department of Experimental Medicine, University of Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy; Centro Universitario per la Ricerca sulla Genomica Funzionale, University of Perugia, Piazza Lucio Severi 1, 06132 Perugia, Italy; Istituto Interuniversitario di Miologia (Interuniversity Institute for Miology), Italy.
Biochim Biophys Acta Mol Cell Res. 2018 May;1865(5):721-733. doi: 10.1016/j.bbamcr.2018.02.010. Epub 2018 Feb 27.
Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocates to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription. In the present review we briefly introduce the Nrf2-Keap1 system and describe Nrf2 functions, illustrate the Nrf2-NF-κB cross-talk, and highlight the effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress.
Nrf2 及其内源性抑制剂 Keap1 作为一种普遍存在的、进化上保守的细胞内防御机制，可对抗氧化应激。在基础条件下，Nrf2 与细胞质中的 Keap1 结合，并被靶向到蛋白酶体降解，以防氧化应激。Nrf2 从 Keap1 上脱离并易位到核内，在核内与小 Maf 蛋白之一形成异二聚体。这些异二聚体识别 AREs，AREs 是 Nrf2 靶基因调节区域中存在的增强子序列，对于转录的关键因子的募集至关重要。在本综述中，我们简要介绍了 Nrf2-Keap1 系统，并描述了 Nrf2 的功能，说明了 Nrf2-NF-κB 的相互作用，并强调了 Nrf2-Keap1 系统在横纹肌组织的生理学和病理生理学中的作用，同时考虑了其在氧化应激和还原应激中的作用。
