Novel aspects of selenium: Glutathione peroxidases protect
against peroxynitrite
Sies, H., Klotz, L.O., Sharov, V.S., Tamler, R., Assmann, A., Briviba, K.
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf,
Postfach 101007, D-40001 Düsseldorf, Germany
GSH peroxidases (GPx) exhibit a novel function, related to the protection against excessive peroxynitrite generation, which can lead to DNA strand-breaks and mutations and to interference with protein tyrosine-based signaling and other protein functions due to formation of 3-nitrotyrosine. GPx protected against the oxidation of dihydrorhodamine 123 (DHR) by peroxynitrite [1]. The maintenance of protection by GPx against peroxynitrite requires GSH as reductant. The reaction is mimicked by GPx mimics, e.g. ebselen [2] or organotellurium compounds [3].
Under steady-state conditions peroxynitrite does not cause the loss of ‘classical’ GPx activity. GPx, like selenomethionine [4], protects against protein 3-nitrotyrosine formation in human fibroblast lysates. The formation of nitrite rather than nitrate from peroxynitrite is enhanced by GPx or by selenomethionine. GPx, and potentially other selenoproteins containing selenocysteine or selenomethionine, thus have a role in GSH-dependent maintenance of a defense line against peroxynitrite-mediated reactions, as a peroxynitrite reductase.
[1] Sies, H., Sharov, V.S., Klotz, L.-O., Briviba, K. (1997) Glutathione Peroxidase Protects against Peroxynitrite-mediated Oxidations: a New Function for Selenoproteins as Peroxynitrite Reductase. J. Biol. Chem. 272: 27812-27817
[2] Sies, H. and Masumoto, H. (1997) Ebselen as a Glutathione Peroxidase Mimic and as a Reactant with Peroxynitrite. Adv. Pharmacol. 38: 229-246
[3] Briviba, K., Tamler, R., Klotz, L.-O., Engman, L., Cotgreave, I.A. and Sies, H. (1998) Protection by organotellurium compounds against peroxynitrite-mediated oxidation and nitration reactions. Biochem. Pharmacol. 55: 817-823
[4] Assmann, A., Briviba, K., and Sies, H. (1998) Reduction of Methionine Selenoxide to Selenomethionine by Glutathione. Arch. Biochem. Biophys. 349: 201-203
| LOCATION |
DATE |
TIME |
| Lecture Hall II |
Wednesday, April 8 |
09:40 am |