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Two‐dimensional database of mouse liver proteins: Changes in hepatic protein levels following treatment with acetaminophen or its nontoxic regioisomer 3‐acetamidophenol
Author(s) -
Fountoulakis Michael,
Berndt Peter,
Boelsterli Urs A.,
Crameri Flavio,
Winter Michael,
Albertini Silvio,
Suter Laura
Publication year - 2000
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/1522-2683(20000601)21:11<2148::aid-elps2148>3.0.co;2-x
Subject(s) - acetaminophen , liver injury , chemistry , enzyme , adduct , pharmacology , proteomics , biochemistry , biology , gene , organic chemistry
Overdose of acetaminophen (APAP) causes acute hepatotoxicity in rodents and man. The mechanism underlying APAP‐induced liver injury remains unclear, but experimental evidence strongly suggests that activation of APAP and subsequent formation of protein adducts are involved in hepatotoxicity. Using proteomics technologies, we constructed a two‐dimensional protein database for mouse liver, comprising 256 different gene products and investigated the proteins affected after APAP‐induced hepatotoxicity. Adult male mice received a single dose of APAP (100 or 300 mg/kg) or its nontoxic regioisomer 3‐acetamidophenol (AMAP, 300 mg/kg). The extent of liver damage was assessed 8 h after administration by increased liver enzyme release and histopathology. Changes in the protein level were studied by comparison of the intensities of the corresponding spots on two‐dimensional (2‐D) gels. The expression level of about 35 of the identified proteins was modified due to treatment with APAP or AMAP. The observed changes were usually in the order of 10—50% of the control value and were more marked in the high‐ than in the low‐dose of APAP‐treated animals. Most of the changes caused by AMAP occurred in a subset of the proteins modified by APAP. Many of the proteins showing changed expression levels are either known targets for covalent modification by N ‐acetyl‐ p ‐benzoquinoneimine (NAPQI) or involved in the regulation of mechanisms that are believed to drive APAP‐induced hepatotoxicity.