PXD047218

PXD047218 is an original dataset announced via ProteomeXchange.

Title	Uncovering the mechanisms responsible for intravenous paracetamol-induced hypotension
Description	Intravenous (IV) administration of paracetamol (APAP) is well-documented to cause severe hypotension, particularly in critically ill patients. We have previously shown that a metabolite of APAP – N-acetyl-p-benzoquinone imine (NAPQI) – is a potent vasodilator, but whether APAP can be metabolised to NAPQI in the vasculature is unknown. Here, we show that NAPQI can be generated by the human coronary endothelial cells (HCAECs) treated with APAP, by staining for APAP-adducts and showing a drop in cell viability and glutathione levels, similar to direct NAPQI treatment. We show that glutathione depletion following APAP treatment is caused the cytochrome p450 enzymes (CYPs) expressed in HCAECs by utilizing a blocker of the CYPs, ketoconazole. Furthermore, mass spectrometry analysis of HCAECs treated with 10 mM APAP for 24h shows upregulation of proteins involved in redox biology and the pentose phosphate pathway, as well as CYP20A1 and POR. Lastly, we show that myeloperoxidase can also metabolize APAP to NAPQI at physiologically relevant concentrations. Taken together, this study shows that APAP can be metabolized within the vasculature to the potent vasodilator NAPQI. We suggest that this is the mechanism by which critically ill patients can present with IV APAP-induced hypotension.
HostingRepository	PRIDE
AnnounceDate	2025-05-20
AnnouncementXML	Submission_2025-05-20_00:49:42.176.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joakim Bastrup
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-24 03:14:17	ID requested
⏵ 1	2025-05-20 00:49:42	announced

10.1016/J.PHRS.2024.107540;

submitter keyword: NAPQI,Acetaminophen, endothelium, CYP20A1, myeloperoxidase, paracetamol

Thomas Jepps
contact affiliation	University of Copenhagen, Department of Biomedical Sciences, Jepps lab, Blegdamsvej 3, Copenhagen N.
contact email	tjepps@sund.ku.dk
lab head
Joakim Bastrup
contact affiliation	Department of Biomedical Sciences, University of Copenhagen, Denmark
contact email	joakimbastrup@hotmail.dk
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/2025/05/PXD047218

PRIDE project URI

• PRIDE
  1. PXD047218
     1. Label: PRIDE project
     2. Name: Uncovering the mechanisms responsible for intravenous paracetamol-induced hypotension