Peroxiredoxins are an ubiquitous family of peroxidases widely distributed among prokaryotes and eukaryotes. Peroxiredoxin 5, which is the last discovered mammalian member, was previously shown to reduce peroxides with the use of reducing equivalents derived from thioredoxin. We report here that human peroxiredoxin 5 is also a peroxynitrite reductase. Analysis of peroxiredoxin 5 mutants, in which each of the cysteine residues was mutated, suggests that the nucleophilic attack on the O-O bond of peroxynitrite is performed by the N-terminal peroxidatic Cys 47 . Moreover, with the use of pulse radiolysis, we show that human peroxiredoxin 5 reduces peroxynitrite with an unequalled high rate constant of (7 % 3) Â 10 7 M À1 s À1 .

Bioluminescence, the emission of ecologically functional light by living organisms, emerged independently on several occasions, yet the evolutionary origins of most bioluminescent systems remain obscure. We propose that the luminescent substrates of the luminous reactions (luciferins) are the evolutionary core of most systems, while luciferases, the enzymes catalysing the photogenic oxidation of the luciferin, serve to optimise the expression of the endogenous chemiluminescent properties of the luciferin. Coelenterazine, a luciferin occurring in many marine bioluminescent groups, has strong antioxidative properties as it is highly reactive with reactive oxygen species such as the superoxide anion or peroxides. We suggest that the primary function of coelenterazine was originally the detoxification of the deleterious oxygen derivatives. The functional shift from its antioxidative to its light-emitting function might have occurred when the strength of selection for antioxidative defence mechanisms decreased. This might have been made possible when marine organisms began colonising deeper layers of the oceans, where exposure to oxidative stress is considerably reduced because of reduced light irradiance and lower oxygen levels. A reduction in metabolic activity with increasing depth would also have decreased the endogenous production of reactive oxygen species. Therefore, in these organisms, mechanisms for harnessing the chemiluminescence of coelenterazine in specialised organs could have developed, while the beneficial antioxidative properties were maintained in other tissues. The full range of graded irradiance in the mesopelagic zone, where the majority of organisms are bioluminescent, would have provided a continuum for the selection and improvement of proto-bioluminescence. Although the requirement for oxygen or reactive oxygen species observed in bioluminescent systems reflects the high energy required to produce visible light, it may suggest that oxygen-detoxifying mechanisms provided excellent foundations for the emergence of many bioluminescent systems.

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Coelenterazine and derivatives were initially considered in the scientific community for their (bio)luminescent properties. Now, another interest of such hetero-bicycles has been pointed out by the discovery of remarkable antioxidative properties, and an unique mode of action as a "cascade": the mother-compound (imidazolopyrazinone) is transformed by ROS into a daughter-compound (2-amino-pyrazine) also endowed with antioxidative properties. This review illustrates the therapeutic potential of synthetic imidazolopyrazinones (coelenterazine analogues): chemical reactivity assays with singulet oxygen, radical anion superoxide, peroxynitrite, and radicals formed during lipid and LDL peroxidation, cellular tests of protection against oxidative stress using keratinocyte, hepatocyte, neuronal and erythrocyte cells, and finally in vivo evaluation in a hamster model of ischemia-reperfusion, are fully described.

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