PXD063467-1

PXD063467 is an original dataset announced via ProteomeXchange.

Title	Comprehensive investigation of (redox-) proteomic changes induced by cana-, dapa-, empagliflozin treatment in cardiac cells
Description	One of the major macrovascular complications that can occur in type 2 diabetes is the development of cardiovascular diseases as for instance heart failure. However, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have shortly after their approval shown to decrease death rates in diabetic patients. Later on, this effect was proven to be independent of the diabetes status of a patient. Interestingly, SGLT-2 is not expressed in cardiac tissue and the underlying mechanisms for these effects remain unclear. In our study we treated two cardiac cell lines (AC16 and HCM) with three different SGLT-2 inhibitors (cana-, dapa and empagliflozin) to investigate their influence on the (redox) proteome. Besides concentrations comparable to those reached in patients (100 nM of cana-, and 10 nM of dapa- or empagliflozin), we also applied a higher dose (10 μM) to check if any effects would be concentration dependent. Furthermore, we included stem-cell derived cardioids on which we mimicked reperfusion injury with the aim to investigate whether and how empagliflozin (20 nM) help to cope with a lack of and subsequent reperfusion with oxygen. These data are included in PRIDE project PXD063242. We were able to show that drug treatments led to higher amounts of glutathione and related thiol metabolites (additionally measured, data not included), presumably showing an increased cellular capacity for handling redox-stress. On the proteome level we were mostly interested in finding shared proteins or redox affected cysteine sites across drugs and systems. For quantitative proteomics we found 21 proteins shared between all 10 μM drug treatments in HCM cells and cardioids, of which 16 showed a consistent expression pattern (downregulation). Among them were glutathione reductase (GSR), peroxiredoxin 2 (PRDX2), ragulator complex protein LAMTOR5 and the catalytic subunit of serine/threonine-protein phosphatase 2A (PP2A). On redox proteome level of HCM cells we detected 54 shared cysteine sites affected by redox changes, among them C423/424 in PKM2, C73 in TXN as well as C100 and C204 in PRDX5, which are the core of its peroxidative activity. All of the mentioned sites were more oxidized upon 10 μM drug treatments. In AC16 cells C93 in MDH2, C127 in PPP1CA and both sites of PRDX5 found in HCM cells as well.
HostingRepository	PRIDE
AnnounceDate	2026-01-21
AnnouncementXML	Submission_2026-01-21_02:45:17.543.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tamara Tomin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	N-ethylmaleimide derivatized cysteine; monohydroxylated residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-29 18:03:43	ID requested
⏵ 1	2026-01-21 02:45:18	announced

10.1016/J.LFS.2025.123923;

submitter keyword: gliflozins,SGLT-2 inhibitors, proteomics, AC16 cells, heart failure, oxidative stress, HCM cells, empagliflozin, redox proteomics, canagliflozin, dapagliflozin

Ruth Birner-Gruenberger
contact affiliation	Institute of Chemical Technologies and Analytics, TU Wien, Austria Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria
contact email	ruth.birner-gruenberger@tuwien.ac.at
lab head
Tamara Tomin
contact affiliation	Senior Scientist at Institute of Chemical Technologies and Analytics Faculty of Technical Chemistry, TU Wien Getreidemarkt 9/164, 1060 Vienna
contact email	tamara.tomin@tuwien.ac.at
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/2026/01/PXD063467

PRIDE project URI

• PRIDE
  1. PXD063467
     1. Label: PRIDE project
     2. Name: Comprehensive investigation of (redox-) proteomic changes induced by cana-, dapa-, empagliflozin treatment in cardiac cells