Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry.

The Journal of Biological Chemistry
Y QiuA L Burlingame

Abstract

Liver toxicity following an overdose of acetaminophen is frequently considered a model for drug-induced hepatotoxicity. Extensive studies over many years have established that such toxicity is well correlated with liver protein arylation by acetaminophen metabolites. Identification of protein targets for covalent modifications is a challenging but necessary step in understanding how covalent binding could lead to liver toxicity. Previous approaches suffered from technical limitations, and thus over the last 10 years heroic efforts were required to determine the identity of only a few target proteins. We present a new mass spectrometry-based strategy for identification of all target proteins that now provides a comprehensive survey of the suite of liver proteins modified. After administration of radiolabeled acetaminophen to mice, the proteins in the liver tissue lysate were separated by two-dimensional polyacrylamide gel electrophoresis. In-gel digestion of the radiolabeled gel spots gave a set of tryptic peptides, which were analyzed by matrix-assisted laser desorption ionization mass spectrometry. Interrogation of data bases based on experimentally determined molecular weights of peptides and product ion tags from postsource ...Continue Reading

References

Nov 15, 1979·Biochemical Pharmacology·D J Miner, P T Kissinger
Feb 14, 1992·Biochemical and Biophysical Research Communications·N R PumfordJ A Hinson
Jan 1, 1992·Drug Metabolism Reviews·N P VermeulenR Van de Straat
Mar 1, 1991·The Biochemical Journal·D J MeyerB Ketterer
May 15, 1991·Archives of Biochemistry and Biophysics·G R HaenenA Bast
Dec 1, 1990·The Biochemical Journal·J D Hayes, C R Wolf
Nov 1, 1990·Seminars in Liver Disease·S D Nelson
Jan 1, 1990·Chemico-biological Interactions·B S AnderssonS Harder
Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·X W WuC T Caskey
Jan 1, 1989·Chemico-biological Interactions·M Comporti
Nov 1, 1989·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J B BartoloneE A Khairallah
Jun 15, 1989·Toxicology and Applied Pharmacology·J B BartoloneE A Khairallah
Sep 1, 1989·Archives of Biochemistry and Biophysics·R R RamsayS D Nelson
Jan 1, 1988·Chemical Research in Toxicology·P J HarvisonS D Nelson
Dec 31, 1987·Biochemical and Biophysical Research Communications·M E KyleJ L Farber
Jan 1, 1988·Chemico-biological Interactions·J Van der ZeeJ Van Steveninck
May 1, 1988·Toxicology and Applied Pharmacology·L L MeyersS D Cohen
Apr 15, 1987·Biochemical Pharmacology·J B BartoloneE A Khairallah
Nov 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·B MannervikH Jörnvall
Feb 15, 1985·Biochemical and Biophysical Research Communications·R J GersonJ L Farber
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D C DahlinS D Nelson
Nov 1, 1983·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S S AnsherE Bueding
Jul 13, 1981·Life Sciences·J A HinsonJ R Gillette
Nov 1, 1995·Journal of Toxicology and Environmental Health·J E ManautouS D Cohen
Jan 1, 1994·Drug Metabolism Reviews·J A HinsonS D Nelson
Sep 1, 1995·Free Radical Biology & Medicine·S Lores ArnaizA Boveris
Oct 1, 1995·Toxicology and Applied Pharmacology·S J BuleraE A Khairallah
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·K R ClauserA L Burlingame

❮ Previous
Next ❯

Citations

Nov 18, 2000·Journal of Biochemical and Molecular Toxicology·F A Nicholls-GrzemskiP C Burcham
Jul 13, 2000·Electrophoresis·S Steiner, F A Witzmann
Jun 27, 2001·Electrophoresis·M FountoulakisL Suter
Mar 7, 2013·Pharmaceutical Research·Mitchell R McGill, Hartmut Jaeschke
Oct 26, 2002·Chemico-biological Interactions·Christine M DieckhausTimothy L Macdonald
Jun 4, 1999·Progress in Biophysics and Molecular Biology·K A Resing, N G Ahn
Feb 13, 2001·Trends in Pharmacological Sciences·E M Gillam
Aug 21, 2003·Toxicology Letters·Hartmut JaeschkeMary Lynn Bajt
Nov 30, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Michael Fountoulakis, Laura Suter
Nov 25, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shufeng Zhou
Jun 29, 2010·Chemical Research in Toxicology·Angela S BurkeJack A Hinson
Feb 19, 2011·Chemical Research in Toxicology·Brendan D StamperSidney D Nelson
Apr 3, 2012·Chemical Research in Toxicology·Yakov M KoenRobert P Hanzlik
Oct 31, 2012·Chemical Research in Toxicology·S Cyrus KhojastehSidney D Nelson
Jul 26, 2012·Chemical Research in Toxicology·Yakov M KoenRobert P Hanzlik
Mar 8, 2013·Chemical Research in Toxicology·Yakov M KoenRobert P Hanzlik
Jun 13, 2008·Chemical Research in Toxicology·Keisuke IkehataRobert P Hanzlik
May 3, 2005·Nature Reviews. Drug Discovery·Daniel C Liebler, F Peter Guengerich
Aug 1, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N R KitteringhamB Kevin Park
Jun 29, 2005·International Journal of Toxicology·F Peter Guengerich
Jun 6, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christine L PowellIvan Rusyn
Jan 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sabrina MoroAngela Mally
Mar 3, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew T LabenskiSerrine S Lau
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·B Kevin ParkDominic P Williams
Mar 21, 2007·BMC Bioinformatics·Robert P HanzlikJianwen Fang
Apr 6, 2006·The AAPS Journal·F Peter Guengerich
Feb 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ehsan KheradpezhouhGrigori Y Rychkov
Nov 28, 2006·Expert Opinion on Drug Metabolism & Toxicology·John Cl Erve
May 26, 2015·Expert Opinion on Drug Metabolism & Toxicology·Mark P Grillo
Nov 27, 2010·Drug Metabolism Reviews·Lizi Zhao, Gisèle Pickering
Nov 24, 2004·Drug Metabolism Reviews·F Peter Guengerich

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.