PXD002590

PXD002590 is an original dataset announced via ProteomeXchange.

Title	Acetaminophen Adducts of Rat Liver Microsomal Proteins using LC-MSMS
Description	The metabolism of xenobiotics in the liver can give rise to reactive metabolites that may covalently bind to tissue macromolecules, such as proteins. Determination of proteins which are targeted by reactive metabolites is of importance in drug discovery and molecular toxicology. However, there are difficulties in the analysis of target proteins in complex biological matrices due to their low abundance. In this study, an analytical approach was developed for systematic identification of the target proteins of acetaminophen (APAP) in rat liver microsomes (RLM) using ultra high-performance liquid chromatography (UHPLC) and high-resolution tandem mass spectrometry. RLM samples were first incubated with and without APAP, digested, and subjected to strong cation exchange (SCX) fractionation prior to the UHPLC-MS/MS analysis. Four data processing strategies were then combined into an efficient label-free workflow, meant to eliminate potential false positives, using peptide spectral matching, statistical differential analysis, product ion screening, and a custom-built delta-mass filtering tool to pinpoint potential modified peptides. This study revealed four proteins, involved in crucial cellular processes, to be covalently modified by APAP.
HostingRepository	PRIDE
AnnounceDate	2015-11-04
AnnouncementXML	Submission_2015-11-04_07:49:08.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lekha Sleno
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-23 00:16:52	ID requested
⏵ 1	2015-11-04 07:49:09	announced

Golizeh M, LeBlanc A, Sleno L, Identification of Acetaminophen Adducts of Rat Liver Microsomal Proteins using 2D-LC-MS/MS. Chem Res Toxicol, 28(11):2142-50(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Drug-Induced Liver Injury, Covalent Binding, High-Resolution Tandem Mass Spectrometry, Rat Liver Microsomes, Acetaminophen, NAPQI, Reactive Metabolites

Lekha Sleno
contact affiliation	Bioanalytical Mass Spectrometry Research Group, Chemistry Department, Université du Québec à  Montréal (UQÀM) Montréal (Québec) Canada
contact email	sleno.lekha@uqam.ca
lab head
Lekha Sleno
contact affiliation	Université du Québec à Montréal (UQÀM), Chemistry Department / Pharmaqam, Montréal, QC, Canada
contact email	sleno.lekha@uqam.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002590
     1. Label: PRIDE project
     2. Name: Acetaminophen Adducts of Rat Liver Microsomal Proteins using LC-MSMS