Possible Mechanisms of ONOO -Mediated Pathology

Nitration of tyrosine is the ONOO reaction pathway of highest yield, primarily due to the ability of SOD to selectively enhance nitration in complex media such as the milieu of a cell. In addition to our work on the nitration pathway, we have recently shown that ONOO reacts quite rapidly (2 X 10 M sec ) (Crow et al., 1995) with zinc-thiolate centers such as those present in numerous transcription factors. Oxidation of such zinc fingers could dramatically alter their ability to recognize and bind DNA. Thus, ONOO could exert significant effects on gene regulation. 

thanks Dr. Larry K. Keefer of the National Cancer Institute for his translation of a German manuscript (Viebel and Mitteil, 1930) dealing with phenolic nitrosation. 

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Beckman, J. S., Ischiropoulos, H., Zhu, L., van der Woerd, M., Smith, C., Chen, J., Harrison, J., Martin, J. C., and Tsai, M. (1992). Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch. Biochem. Biophys. 298, 438-445. 

Beckman, J. S., Ye, Y. Z., Anderson, P. G., Chen, J., Accavitti, M. A., Tarpey, M. M., and White, C. R. (1994). Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol. Chem. Hoppe-Seyler 375, 81-88. 

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