<p class="first" id="d8078071e79">'Reactive oxygen species' (ROS) is an umbrella term
for an array of derivatives of
molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation
of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here
we focus on ROS at physiological levels and their central role in redox signalling
via different post-translational modifications, denoted as 'oxidative eustress'. Two
species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key
redox signalling agents generated under the control of growth factors and cytokines
by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial
electron transport chain. At the low physiological levels in the nanomolar range,
H2O2 is the major agent signalling through specific protein targets, which engage
in metabolic regulation and stress responses to support cellular adaptation to a changing
environment and stress. In addition, several other reactive species are involved in
redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids.
Recent methodological advances permit the assessment of molecular interactions of
specific ROS molecules with specific targets in redox signalling pathways. Accordingly,
major advances have occurred in understanding the role of these oxidants in physiology
and disease, including the nervous, cardiovascular and immune systems, skeletal muscle
and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination
of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting
disease initiation and progression in clinical trials. However, controlling specific
ROS-mediated signalling pathways by selective targeting offers a perspective for a
future of more refined redox medicine. This includes enzymatic defence systems such
as those controlled by the stress-response transcription factors NRF2 and nuclear
factor-κB, the role of trace elements such as selenium, the use of redox drugs and
the modulation of environmental factors collectively known as the exposome (for example,
nutrition, lifestyle and irradiation).
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