Reactive Oxygen Species: Drivers of Physiological and Pathological Processes.
Reactive Oxygen Species: Drivers of Physiological and Pathological Processes.
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DOI：
10.2147/jir.s275595
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发表时间：
2020
影响因子：
4.5
通讯作者：
Aran JM
中科院分区：
文献类型：
--
作者：
Checa J;Aran JM
自从大约24亿年前的大氧化事件以来，地球就沉浸在氧化的大气中。因此，已经提出，过量的氧，最初是光合蓝藻的废物，诱导氧化应激和活性氧（ROS）的产生，这已经成为生物进化和真核发生的基本驱动力。事实上，在生物体的整个生命周期中，ROS直接（作为诱变剂）或间接（作为信使和调节剂）影响细胞的所有结构和功能成分，以及细胞生物学的许多方面。无论是否受到保护性抗氧化系统的抑制，过量的ROS不仅会导致基因组突变，还会诱导蛋白质（蛋白质氧化和过氧化）、脂质和聚糖（高级脂氧化和糖化终产物）的不可逆氧化修饰，损害其功能并促进疾病或细胞死亡。相反，低水平的局部ROS作为氧化还原信号分子在参与维持细胞稳态的广泛途径（MAPK/ERK、PTK/PTP、PI 3 K-AKT-mTOR）和调节关键转录因子（NFκB/IκB、Nrf 2/KEAP 1、AP-1、p53、HIF-1）中发挥重要作用。因此，ROS可以塑造多种细胞功能，包括增殖、分化、迁移和凋亡。在这篇综述中，我们将简要概述ROS在生理和病理过程中的相关性，特别是炎症和衰老。深入了解活性氧驱动的分子机制及其在稳态和压力条件下的影响将为新型治疗干预措施的开发铺平道路。这将减轻ROS在各种慢性炎症和年龄相关疾病的发作和进展中的有害结果。
Since the Great Oxidation Event, about 2.4 billion years ago, the Earth is immersed in an oxidizing atmosphere. Thus, it has been proposed that excess oxygen, originally a waste product of photosynthetic cyanobacteria, induced oxidative stress and the production of reactive oxygen species (ROS), which have since acted as fundamental drivers of biologic evolution and eukaryogenesis. Indeed, throughout an organism’s lifespan, ROS affect directly (as mutagens) or indirectly (as messengers and regulators) all structural and functional components of cells, and many aspects of cell biology. Whether left unchecked by protective antioxidant systems, excess ROS not only cause genomic mutations but also induce irreversible oxidative modification of proteins (protein oxidation and peroxidation), lipids and glycans (advanced lipoxidation and glycation end products), impairing their function and promoting disease or cell death. Conversely, low-level local ROS play an important role both as redox-signaling molecules in a wide spectrum of pathways involved in the maintenance of cellular homeostasis (MAPK/ERK, PTK/PTP, PI3K-AKT-mTOR), and regulating key transcription factors (NFκB/IκB, Nrf2/KEAP1, AP-1, p53, HIF-1). Consequently, ROS can shape a variety of cellular functions, including proliferation, differentiation, migration and apoptosis. In this review, we will give a brief overview of the relevance of ROS in both physiological and pathological processes, particularly inflammation and aging. In-depth knowledge of the molecular mechanisms of ROS actuation and their influence under steady-state and stressful conditions will pave the way for the development of novel therapeutic interventions. This will mitigate the harmful outcomes of ROS in the onset and progression of a variety of chronic inflammatory and age-related diseases.