Rampon Christine, Volovitch Michel, Joliot Alain, Vriz Sophie
Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, 75231 Paris, France.
Sorbonne Paris Cité, Univ Paris Diderot, Biology Department, 75205 Paris CEDEX 13, France.
Antioxidants (Basel). 2018 Nov 6;7(11):159. doi: 10.3390/antiox7110159.
Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS, endowed with signalling properties, are mainly produced by NADPH oxidases (NOXs) at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differ in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic, in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetic processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function, as well as pharmacological strategies, have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.
活性氧(ROS)最初被归类为完全有害的化合物,但近年来,鉴于其作为信号分子的作用,人们对它的兴趣与日俱增。ROS作用的主要靶点是半胱氨酸的可逆氧化,导致二硫键的形成,从而调节蛋白质的构象和活性。具有信号特性的ROS主要由质膜上的NADPH氧化酶(NOXs)产生,但其作用还涉及多个对氧化还原敏感的蛋白质家族组成的复杂机制,这些家族在亚细胞定位和活性方面存在差异。鉴于ROS的水平和分布具有高度动态性,部分原因是其稳定性有限,各种荧光ROS传感器的开发,其中一些是定量的(比率型),代表了该领域的一项重大突破,并且已适用于体外和体内应用。ROS信号传导的生理意义将主要在形态发生过程、胚胎发育、再生和干细胞分化的框架内进行阐述。功能获得和功能丧失以及药理学策略已经证明,在这些过程的多个阶段,ROS信号传导具有广泛但特定的需求,以及它与其他知名信号通路的复杂关系。