Touati D
Laboratoire de Gén ique Moléculaire des Réponses Adaptatives, Institut Jacques Monod, CNRS-Université Paris 6, France.
Redox Rep. 2000;5(5):287-93. doi: 10.1179/135100000101535825.
Reactive oxygen species (ROS) are produced as an inescapable consequence of aerobic life. Their levels are kept low enough to be harmless by specific enzymes, such as superoxide dismutase, which eliminate them. Expression of these defence enzymes is modulated depending on the environmental oxidative threat. This basic protection, however, is not sufficient to protect against sudden large increases in ROS production. To cope with oxidative stress, rapid global responses are induced that enable bacteria to survive the stress period by multiple means: elimination of ROS, repair of oxidative damage, bypass of damaged functions and induction of adapted metabolism. The soxRS response, which protects against superoxide (O2.-)-generating agents and nitric oxide (.NO), is triggered by activation of a sensor molecule, SoxR, containing two essential [2Fe-2S] clusters. The soxRS regulon is induced in a two-stage process. Upon activation, SoxR induces soxS expression and SoxS, in turn, activates transcription of genes of the regulon. The mechanism of signalling has been under debate for years. Evidence for several pathways of SoxR activation, mediated by the modifications of [2Fe-2S] centres, has emerged from recent data. The direct oxidation of [2Fe-2S] centres, any event that may interfere with the pathway maintaining SoxR in a reduced inactive form, and direct nitrosylation by .NO can trigger SoxR activation. The multiple possibilities for SoxR activation, along with signal amplification via the two-stage process, constitute a unique, and particularly sensitive, system enabling cells to induce rapidly a protective response to a broad range of environmental changes indicative of possible oxidative stress.
活性氧(ROS)是有氧生命不可避免的产物。它们的水平通过超氧化物歧化酶等特定酶保持在足够低的无害水平,这些酶可消除ROS。这些防御酶的表达会根据环境氧化威胁进行调节。然而,这种基本保护不足以抵御ROS产生的突然大幅增加。为了应对氧化应激,会诱导快速的全局反应,使细菌能够通过多种方式在应激期存活下来:消除ROS、修复氧化损伤、绕过受损功能以及诱导适应性代谢。soxRS反应可抵御产生超氧化物(O2.-)的试剂和一氧化氮(.NO),它由含有两个必需的[2Fe - 2S]簇的传感器分子SoxR激活引发。soxRS调节子通过两阶段过程被诱导。激活后,SoxR诱导soxS表达,而SoxS反过来激活调节子基因的转录。多年来,信号传导机制一直存在争议。最近的数据显示了由[2Fe - 2S]中心修饰介导的SoxR激活的几种途径的证据。[2Fe - 2S]中心的直接氧化、任何可能干扰将SoxR维持在还原非活性形式的途径的事件以及由.NO进行的直接亚硝基化都可以触发SoxR激活。SoxR激活的多种可能性,以及通过两阶段过程的信号放大,构成了一个独特且特别敏感的系统,使细胞能够快速诱导对广泛的环境变化的保护反应,这些变化表明可能存在氧化应激。