Evidence for common binding of acetaminophen and bromobenzene to the 58-kDa acetaminophen-binding protein.
Acetaminophen (APAP) toxicity has been closely associated with covalent binding to a cytosolic protein of approximately 58 kDa (58-ABP). To determine if metabolites of other toxicants might also selectively target this protein, studies were conducted with bromobenzene (BrB). Mice were given phenobarbital (80 mg/kg/d x 4 d) and were killed 4 h after challenge with 800 mg BrB/kg. Liver cytosols from BrB-treated or naive mice were incubated with an APAP activating system. Cytosolic fractions were analyzed for APAP binding by Western blotting with anti-APAP antibody. Binding to 58-ABP was selectively decreased in liver cytosol from BrB-treated mice while binding to other targets was minimally affected. Western blotting of the same samples with anti-58-ABP antisera showed that this decrease in binding did not result from diminished 58-ABP content. HPLC analysis of APAP-N-acetyl cysteine conjugate formation in vitro indicates that APAP activation was not altered in the incubates with cytosol from BrB-treated mice. These results suggest that the 58-ABP may be a common target for electrophiles in reactive intermediate toxicity.
D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D001969:Bromobenzenes / Q000008:administration & dosage / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D051137:Selenium-Binding Proteins
D001969:Bromobenzenes; D002352:Carrier Proteins; C495177:Selenbp2 protein, mouse; D051137:Selenium-Binding Proteins; D000082:Acetaminophen; C032036:bromobenzene