PXD027674

PXD027674 is an original dataset announced via ProteomeXchange.

Title	Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS
Description	Acetaminophen (N-acetyl-p-aminophenol; APAP) is a mild analgesic and antipyretic used commonly worldwide. Although APAP is considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), to proteins. The aim of this in vivo study was to identify APAP-protein targets in both rat and mouse liver, and to compare the results from both species, using bottom-up proteomics and targeted multiple reaction monitoring (MRM) experiments. Livers from rats and mice, treated with APAP, were homogenized and digested by trypsin. Digests were then fractionated by mixed-mode solid-phase extraction prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) using scheduled multiple reaction monitoring (MRM) acquisition. The targeted assays were optimized based on high-resolution MS/MS data from information-dependent acquisition (IDA) using control liver homogenates treated with a custom alkylating reagent forming a positional isomer of the APAP modification on all cysteine residues, in order to build an in-house modified peptide database for targeted analysis. A list of putative in vivo targets of APAP were screened from previous in vitro studies, data-dependent high-resolution MS/MS analyses of liver digests, as well as selected proteins from the target protein database (TPDB), an online resource which references previous reports of proteins found to be modified by acetaminophen. Multiple protein targets of APAP in each species were found, while confirming modification sites.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:56:16.010.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027674
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Lekha Sleno
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-30 04:46:08	ID requested
⏵ 1	2022-02-17 05:56:16	announced

Geib T, Moghaddam G, Supinski A, Golizeh M, Sleno L, Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS. Front Chem, 9():736788(2021) [pubmed]

submitter keyword: Acetaminophen, Covalent binding, NAPQI, reactive metabolite, rat, mouse, liver

Lekha Sleno
contact affiliation	Chemistry department, University of Quebec at Montreal (UQAM)
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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD027674

PRIDE project URI

• PRIDE
  1. PXD027674
     1. Label: PRIDE project
     2. Name: Protein Targets of Acetaminophen Covalent Binding in Rat and Mouse Liver Studied by LC-MS/MS