Signaling Functions of Free Radicals Superoxide & Nitric Oxide under Physiological & Pathological Conditions
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Superoxide and nitric oxide are ubiquitous physiological free radicals that are responsible for many pathological disorders. Both radicals by themselves are relatively harmless but are the precursors of many toxic species such as peroxy and hydroxyl radicals, hydrogen peroxide, and peroxynitrite. However, it has been shown now that both superoxide and nitric oxide are also able to perform important signaling functions in physiological and pathophysiological processes. Wrongly named “superoxide,” the radical anion of dioxygen is not a super-oxidant but the strong super-nucleophile, an efficient catalyst of heterogenic nucleophilic reaction. Due to this, superoxide plays an important role in many enzymatic processes such as the phosphorylation and activation of numerous protein kinases. On the other hand, superoxide inhibits the activation of phosphatases, the enzymes catalyzed by dephosphorylation of protein kinases. We suggest that superoxide catalyzes these enzymatic processes as a result of its nucleophilic properties. Another important physiological function of superoxide and nitric oxide is their competition for the interaction with mitochondrial cytochrome c oxidase. Disturbance of superoxide/nitric oxide balance leads to the dysfunction of mitochondria and the enhancement of apoptosis and oxidative stress, which are primary causes of various pathological disorders and aging. In conclusion, interplay between superoxide and nitric oxide, one of major factors of aging development, is considered.
KeywordsSuperoxide Nitric oxide Protein kinases Aging
- 2.Moreno-Manzano, V., Ishikawa, Y., Lucio-Cazana, J., & Kitamura, M. (2000) Selective involvement of superoxide anion, but not downstream compounds hydrogen peroxide and peroxynitrite, in tumor necrosis factor-alpha-induced apoptosis of rat mesangial cells. The Journal of Biological Chemistry, 275, 12684–12691.PubMedCrossRefGoogle Scholar
- 9.Di Massimo, C., Scarpelli, P., Lorenzo, N. D., Caimi, G., Orio, F. D., & Ciancarelli, M. G. (2005) Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age. Life Science, 78, 1163–1167.Google Scholar
- 10.Adler, A., Messina, E., Sherman, B., Wang, Z., Huang, H., Linke, A., & Hintze, T. H. (2003) NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats. American Journal of Physiology. Heart and Circulatory Physiology, 285, H1015–H1022.PubMedGoogle Scholar