REDOX SIGNALLING BY TRANSCRIPTION FACTORS NF-KB AND AP-l IN LYMPHOCYTES

When molecular oxygen accumulated in our atmosphere more than 2 billion years ago, aerobic organisms adapted using using oxygen as an electron acceptor in respiration. Although respiration is, by far, one of the most efficient ways of generating energy in biological systems, it has one harmful side-effect: incomplete reduction of dioxygen results in the formation of ROIs. § These include the superoxide anion (02 .-), hydrogen peroxide (H20 2), and the hydroxyl radical (OH·). Superoxide anions originate from a single electron transfer on dioxygen [I]. This ROI has a short diffusion radius inside the cell, but it is eventually converted by SODs into H20 2, the most stable and diffusible ROI. Transition metals, such as iron or copper ions, convert O2.and H20 2 to an extremely reactive hydroxyl radical via the Fenton or Haber/Weiss reaction. While low amounts of ROIs can be considered as physiological side-products of various electron transfer reactions and are tolerated by the cell, increased levels of ROIs, referred to as oxidative stress, are linked to pathophysiological phenomena. Many adverse conditions, including ionizing and UV irradiation, heat shock, viral and bacterial infections, as well as environmental pollutants cause oxidative stress. In principle, ROIs can react with all classes of biological macromolecules, resulting in lipid peroxidation, inactivation of proteins, and strand breakage in nucleic acids [I]. During evolution, cells of the immune system, in particular, have learned to utilize ROIs in two ways: first, as chemical weapons and, second, as signalling molecules triggering a variety of biological processes, such as gene expression and proliferation control. How macrophages and neutrophils produce high amounts of ROIs as a first line of defense against invading microorganisms has been reviewed extensively [2, 3]. However, the roles of ROIs as signalling molecules are just beginning to be discovered. On the one hand, immune cells but also