TOXI 76 |
| Hydroquinone (HQ) and its glutathione conjugates (GSHQs) cause renal cell necrosis by redox-cycling and adducting macromolecules, specifically in the S3 segment of the renal proximal tubules. Recent technological advancements allow for the detection of chemical-induced post-translational modifications (PTMs) that may alter cell signaling pathways or alter the structure and function of the modified proteins. We have identified such modified proteins following administration of 2-(glutathion-S-yl)HQ (GSHQ) (400µmol/kg, iv, 2hr) to Long-Evans rats. Four proteins were adducted by 2-(Cystein-S-yl)HQ (CSHQ), and 3 proteins adducted by HQ. The HQ adduct originates as a quinol-thioether adduct and then the thioether bond hydrolyzes during the protein digestion leaving just the HQ adducted. The instability of the thioether bond may explain why no C adducts are observed. The adducts are observed on K, R, and E. The site-specific identification of covalently adducted proteins is a prerequisite for understanding the biological significance of chemical-induced PTMs and the subsequent toxicological response. |
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Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster
Division of Chemical Toxicology |