caa a22 4500 378874306 CHVBK 20180305123416.0 cr unu---uuuuu 161128e20030220xx s 000 0 eng 10.1515/BC.2003.026 doi (NATIONALLICENCE)gruyter-10.1515/BC.2003.026 Modifications of Glyceraldehyde-3-PhosphateDehydrogenase Induced by IncreasingConcentrations of Peroxynitrite:Early Recognition by 20S Proteasome [Elektronische Daten] [D.P. Buchczyk, T. Grune, H. Sies, L.-O. Klotz] Peroxynitrite, a potent oxidizing and nitrating species, induces covalent modifications of biomolecules in a number of pathological conditions. In previous studies with S. cerevisiae, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as being especially susceptible to nitration by peroxynitrite. The activity of this enzyme was strongly inhibited by low doses of peroxynitrite in yeast and in cultured rat astrocytes. Here, the sequence of modifications of isolated mammalian GAPDH induced by increasing concentrations of peroxynitrite is demonstrated to be as follows: (i) oxidation, leading to inactivation and to enhanced susceptibility of GAPDH for proteasomal degradation, (ii) oligomer formation, and (iii) nitration. In our study the susceptibility for degradation by isolated 20S proteasome was by far the most sensitive parameter for peroxynitrite-induced damage to GAPDH, implying that this might also occur under pathological conditions where peroxynitrite is generated at low concentrations in vivo. Copyright © 2003 by Walter de Gruyter GmbH & Co. KG Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence Buchczyk D.P. aut Grune T. aut Sies H. aut Klotz L.-O aut Biological Chemistry Walter de Gruyter 384/2(2003-02-20), 237-241 1431-6730 384:2<237 2003 384 bchm https://doi.org/10.1515/BC.2003.026 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2003.026 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Buchczyk D.P. aut NATIONALLICENCE 700 1- Grune T. aut NATIONALLICENCE 700 1- Sies H. aut NATIONALLICENCE 700 1- Klotz L.-O aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 384/2(2003-02-20), 237-241 1431-6730 384:2<237 2003 384 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter