title: Peroxiredoxin 6 is a molecular target for 1,2-naphthoquinone, an atmospheric electrophile, in human pulmonary epithelial A549 cells.
abstract: 1,2-Naphthoquinone (1,2-NQ) is an electrophile found in the atmosphere, which reacts readily with protein nucleophiles to form a stable protein adduct. Peroxiredoxin 6 (Prdx6) is predominantly expressed in lung tissue and functions in antioxidant defense by facilitating the repair of damaged cell membranes via reduction of peroxidized phospholipids. In the present study, human A549 pulmonary epithelial cells were exposed to 1,2-NQ to explore whether 1,2-NQ can bind covalently to Prdx6, thereby disrupting its catalytic activity. Two-dimensional SDS/PAGE followed by western blot analysis with a specific antibody against 1,2-NQ showed that Prdx6 was covalently modified by 1,2-NQ. Using purified human Prdx6, it was found that 1,2-NQ bound covalently to Prdx6 through Cys47, Lys144 and Cys91, resulting in a significant reduction in phospholipase A(2) activity. These results suggest that arylation of Prdx6 by 1,2-NQ may, at least in part, be involved in the cellular toxicity induced by 1,2-NQ.
authors: Naoyuki
authors: N
authors: Takayama
authors: Noriko
authors: N
authors: Iwamoto
authors: Daigo
authors: D
authors: Sumi
authors: Yasuhiro
authors: Y
authors: Shinkai
authors: Toshiko
authors: T
authors: Tanaka-Kagawa
authors: Hideto
authors: H
authors: Jinno
authors: Yoshito
authors: Y
authors: Kumagai
mesh_terms: D000393:Air Pollutants / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D013058:Mass Spectrometry; D009285:Naphthoquinones / Q000378:metabolism*; D054465:Peroxiredoxin VI / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000393:Air Pollutants; D009285:Naphthoquinones; C040756:1,2-naphthoquinone; D054465:Peroxiredoxin VI; D054467:Phospholipases A2