%0 Journal Article
%T Nuclear Transport: A Switch for the Oxidative Stress〞Signaling Circuit?
%A Mohamed Kodiha
%A Ursula Stochaj
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/208650
%X Imbalances in the formation and clearance of reactive oxygen species (ROS) can lead to oxidative stress and subsequent changes that affect all aspects of physiology. To limit and repair the damage generated by ROS, cells have developed a multitude of responses. A hallmark of these responses is the activation of signaling pathways that modulate the function of downstream targets in different cellular locations. To this end, critical steps of the stress response that occur in the nucleus and cytoplasm have to be coordinated, which makes the proper communication between both compartments mandatory. Here, we discuss the interdependence of ROS-mediated signaling and the transport of macromolecules across the nuclear envelope. We highlight examples of oxidant-dependent nuclear trafficking and describe the impact of oxidative stress on the transport apparatus. Our paper concludes by proposing a cellular circuit of ROS-induced signaling, nuclear transport and repair. 1. Introduction 1.1. Reactive Oxygen Species Oxidative stress is generated by an increase in reactive oxygen species (ROS), either in the form of free radicals or nonradical oxidants [1, 2]. Although elevated levels of ROS can damage a wide variety of molecules, ROS production is essential to normal cell physiology [3每12]. As such, ROS participate in cell-signaling events and can function as second messengers. Moreover, ROS are generated at sites of inflammation, where they fend off microbial infections [13每16]. On the other hand, ROS are believed to contribute to aging [3每9, 12]; they are also produced in response to environmental insults, such as X-rays, UV light, ultrasound, or microwave radiation [17每19]. At the cellular level, ROS are generated as metabolic byproducts of normal biological processes, with oxidative phosphorylation in mitochondria as the primary source in eukaryotic cells [20]. Aside from the mitochondrial electron transport chain, NADPH oxidases, cyclooxygenases, lipoxygenases, xanthine oxidase, and other cellular enzymes make also important contributions to cellular ROS production [21每25]. The different types of ROS and their mode of action have been discussed in detail [1, 11, 26每30]. ROS that are particularly important to cell physiology include the hydroxyl radical ˋOH, superoxide anion ˋ O 2 ˋ , the nonradical hydrogen peroxide (H2O2), alkoxy and peroxy radicals, hypochlorous acid or peroxynitrite, and reactive sulfur species [1, 29, 31, 32]. Here, we recapitulate the properties of those ROS only that are relevant to the experiments discussed in this review. The hydroxyl
%U http://www.hindawi.com/journals/jst/2012/208650/