For Scientists

Oxidative stress, an excess of radicals and other reactive oxygen species (Ros) relative to antioxidant defence, has been suggested as a major disease mechanism from single cell to multicellular organisms. With the idea to overcome this, antioxidants are heavily marketed, yet without proof of their effectiveness. Rather, evidence suggests adverse effects. This paradox is due to the fact that ROS are not only ‘bad’, but – in tightly regulated amounts – also act as essential signalling molecules and are essential for host defence. In a tightly controlled fashion ROS regulate for example proliferation, differentiation, metabolic actions, apoptosis and angiogenesis. Moreover, a deficiency in ROS can result in similarly harmful reductive stress. Thus, the roles of ROS in physiology and pathophysiology need to be completely re-defined and much better understood before safe applications are possible. Unravelling the fine balance between ROS acting as a friend or a foe is fundamental to understand aerobic life. To advance this important area of biology and medicine, highly synergistic approaches combining diverse and scattered disciplines are needed. EU-ROS brings together multi-disciplinary experts to enhance the competitiveness of European research. By applying fundamentally new approaches EU-ROS generates advanced knowledge and translate this into novel applications ranging from medicine to crop science. With its dynamic structure, EU-ROS is open for further experts. This COST Action supports capacity building by future European research leaders and talented women. Collectively, EU-ROS overcomes the fragmentation of European R&D on oxygen/ROS research while its translational components contribute to European societies’ economic growth and wellbeing.

EU-ROS has created a unique network of highly interdisciplinary researchers who have made substantial contributions to the understanding of redox (patho-)physiology. The network includes groups from academia and industry with broad interdisciplinary and synergistic knowledge. EU-ROS is innovative in several aspects, for example by:

EU-ROS forms a dedicated network of leading European researchers and stakeholders. Indeed, a major advantage of EU-ROS is its flexible and open structure and multidisciplinary participation including a unique starter array of experts from basic to and applied research, from academia and industries. They combine their expertise in order to not only provide major insights into the exciting field of redox biology and pathology but also into its clinical applications. EU-ROS provides not only scientific, but also –in the longer term – societal benefits by contributing for example to consumer information and the sustainability of European health care systems.

Mechanisms of endothelial and smooth muscle dysfunction with special emphasis on redox processes and oxidative stress for known cardiovascular risk factors. Potential targets of pharmacological compounds to suppress oxidative stress and progression of the disease or cardiovascular complications. Karbach et al. Curr. Pharm. Des 2014. With permission of Bentham Science Publishers.

In a number of pathological conditions, such as inflammation, type 2 diabetes, cardiovascular diseases, stroke and cancer, producers of ROS – that are part of the normal cellular signal transduction system – are activated. Several of these ROS sources are addressed by EU-ROS, for example, the NADPH oxidase family, mitochondria, uncoupled nitric oxide synthase (NOS), xanthine oxidase, P450 enzymes and myeloperoxidases. NADPH oxidases stand out from other ROS sources as NOX are the only enzymes with the sole function to generate ROS. Seven NOX isoforms exist that demonstrate cell-specificity, differences in sub-cellular localization and regulation. They serve essential physiological roles, e.g. in host defence, cell proliferation, differentiation, adhesion, metabolic action and apoptosis. However, there is convincing evidence of detrimental effects of excessive ROS production by NOX in various diseases. An underexplored area, which is addressed by the synergistic strategy of this COST Action, is the cross talk between different sources of ROS. NADPH oxidases may be initial sources that render other enzymes dysfunctional, which then become ROS sources themselves.

Oxidative stress is not only relevant in mammals, but also for example in plants. For example, similar enzymes appear to be involved. Oxidative stress is also considered as part of plants’ response to environmental constraints. As a consequence of plant aerobic metabolic processes, such as respiration and photosynthesis, ROS are produced. Also in plants, ROS are key components in fundamental plant processes, such as stomatal closure, response to environmental changes or gene expression and modulation of protein activity. Similar to mammals plant have NADPH oxidases, the respiratory burst oxidase homologues (RBOHs). The tight regulation of RBOH activity makes these proteins good candidates for the fine-tuning of ROS production in crop science. For example, the role of ROS in the legume Rhizobium symbiosis has been highlighted. Legumes are the only plant family with the ability to establish a symbiotic interaction with soil bacteria, rhizobia, leading to the formation of a new organ, the root nodule, whose primary function is dinitrogen (N2) fixation. This symbiotic interaction is crucial as (i) legumes are important for food and feed and (ii) biological N2 fixation is a key component of sustainable agriculture as it strongly limits the use of costly fertilizers and the water pollution they induce.

Despite these recent progresses, many fundamental questions and interrelations of these observations still remain unanswered. One reason is the urgent need for potent and specific research tools, such as animal models and antibodies, as well as specific pharmacological reagents. Mutual access to these would allow scientists to test the oxidative stress hypothesis in an unprecedented manner. Importantly, this Action provides a unique opportunity not only to develop such tools and reagents, but also to establish their efficacy in multiple systems and providing a proof of concept in multiple organisms and disease models. Indeed, a structured public platform for exchanging the respective information will be a major step forward in translating the oxidative stress hypothesis into clinical application.