title: Responses to peroxynitrite in yeast: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a sensitive intracellular target for nitration and enhancement of chaperone expression and ubiquitination.
abstract: Peroxynitrite (ONOO-), a potent oxidizing and nitrating species, has been linked to covalent modifications of biomolecules in a number of pathological conditions. In S. cerevisiae, a model eukaryotic cell system, ONOO- was found to be more potent than hydrogen peroxide in oxidizing thiols, inducing heat shock proteins (Hsp70) and enhancing the ubiquitination of proteins. As identified by microsequence analysis following immunoprecipitation with anti-nitrotyrosine antibodies, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was especially susceptible to nitration by ONOO- in yeast cells. The activity of this enzyme was strongly inhibited upon steady-state exposure of the cells to low doses of ONOO- in yeast and in cultured rat astrocytes. Thus, ONOO- is a potent stressor in yeast capable of inducing oxidative damage and protein nitration, with GAPDH being a preferential target protein that is efficiently inactivated.
authors.affiliation: Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
authors.forename: D P
authors.initials: DP
authors.lastname: Buchczyk
authors.forename: K
authors.initials: K
authors.lastname: Briviba
authors.forename: F U
authors.initials: FU
authors.lastname: Hartl
authors.forename: H
authors.initials: H
authors.lastname: Sies
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004228:Dithionitrobenzoic Acid; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000187:drug effects / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000187:drug effects; D009566:Nitrates / Q000494:pharmacology* / Q000633:toxicity; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013439:Sulfhydryl Reagents; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism; D014452:Ubiquitins / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D009566:Nitrates; D016877:Oxidants; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D014452:Ubiquitins; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D004228:Dithionitrobenzoic Acid; D006861:Hydrogen Peroxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases