کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911168 1046804 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Redox cycling of 9,10-phenanthraquinone to cause oxidative stress is terminated through its monoglucuronide conjugation in human pulmonary epithelial A549 cells
چکیده انگلیسی
9,10-Phenanthraquinone (PQ), a component of airborne particulate matter, causes marked cellular protein oxidation and cytotoxicity through a two-electron reduction to 9,10-dihydroxyphenanthrene (PQH2), which is associated with the propagation of reactive oxygen species (K. Taguchi et al., Free Radic. Biol. Med. 43:789-799, 2007). In the present study, we explored a biotransformation pathway for the detoxification of PQ. Exposure of human pulmonary epithelial A549 cells to PQ resulted in a time-dependent appearance of an unknown metabolite in the medium that was identified as the monoglucuronide of PQH2 (PQHG). Whereas a variety of isozymes of uridine 5′-diphosphate glucuronosyltransferase (UGTs) are responsible for PQHG formation, UGT1A10 and UGT1A6 were particularly effective catalysts for glucuronide conjugation. In cell-free systems, PQ exhibited a rapid thiol oxidation and subsequent oxygen consumption in the presence of dithiothreitol, whereas PQHG did not. Unlike the parent compound, PQHG completely lost the ability to oxidize cellular proteins and cause cell death in A549 cells. In addition, deletion of the transcription factor Nrf2 decreased PQHG formation and increased PQ-mediated toxicity of mouse primary hepatocytes. Thus, we conclude that PQHG is a metabolite of PQ, generated through PQH2, that terminates its redox cycling and transports it to extracellular space.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 44, Issue 8, 15 April 2008, Pages 1645-1655
نویسندگان
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