Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.
Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.
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DOI：
10.1016/j.redox.2015.06.012
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发表时间：
2015-08
期刊：
影响因子：
11.4
通讯作者：
Manea A
中科院分区：
文献类型：
--
作者：
Manea SA;Constantin A;Manda G;Sasson S;Manea A
NADPH 氧化酶 (Nox) 代表异源寡聚酶家族，其独特的生物学功能是产生活性氧 (ROS)。 Nox 衍生的 ROS 是信号转导途径的重要调节剂，控制细胞生长、增殖、迁移、分化和凋亡、免疫反应和生化途径等关键生理活动。 Nox 衍生的 ROS 形成增强，通常与不同 Nox 亚型的上调有关，已在多种病理学中得到证实，即心血管疾病、糖尿病、肥胖、癌症和神经退行性疾病。 Nox 衍生的 ROS 的有害影响与细胞信号传导的改变和/或核酸、蛋白质、碳水化合物和脂质的直接不可逆氧化损伤有关。因此，人们对 Nox 酶的转录调控机制进行了广泛的研究，试图找到抵消各种病理状态下 Nox 衍生 ROS 过度形成的方法。尽管已有大量数据，但导致 Nox 上调的分子途径尚未完全了解。本文总结了与血管病理生理学中 Nox 表达调节相关的一些最新进展和概念。它强调了转录因子和表观遗传机制在此过程中的作用。 Nox 上调与心血管功能障碍的发生和发展相关，鉴定参与 Nox 上调的信号分子可能有助于开发治疗心血管疾病的新策略。 Nox 是一类独特的酶，其唯一功能是产生 ROS。 Nox 衍生的 ROS 在细胞生理学中发挥着重要作用。据报道，在许多病理学中，Nox 的表达和激活增强。 Nox 表达通过复杂的转录因子表观遗传机制进行调节。了解 Nox 调节对于抵消 ROS 诱导的细胞损伤至关重要。
NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases. Nox is a unique class of enzymes whose sole function is the generation of ROS. Nox-derived ROS play a major role in cell physiology. Enhanced expression and activation of Nox has been reported in numerous pathologies. Nox expression is regulated via complex transcription factor-epigenetic mechanisms. Understanding of Nox regulation is essential to counteract ROS-induced cell damage.