| Research Abstract |
Although reactive oxygen and nitrogen species have been postulated to underlie the pathogenesis, molecular mechanism and effective way to inhibit oxygen toxicity are not known. The aim of the present study is to synthesize specific enzymes and related inhibitors which can be targeted to the site of generation of the reactive species, thereby clarifying physiological and pathological roles of the reactive species. kinetic experiments using these site-directed molecular probes revealed that cross-talk between molecular oxygen, nitric oxide (NO) and superoxide radicals constitutes a supersystem that plays critical roles in the regulation of embryonic development, circulation, energy metabolism defense system for pathogens, and mitochondria-dependent programmed cell death. The supersystem also plays critical roles in the metamorphosis of tadpoles to fogs and their changes in nitrogen metabolism, such as improvement of urea cycle, a prerequisite to their transformation from vegetarian to carnivore. The results also indicated that the supersystem also underlies the pathogenesis of side effects of anticancer agents in the kidney and gastrointestinal tracts. We succeeded to develop an effective method for inhibiting the side effects by modulating the supersystem.
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