PXD025516

PXD025516 is an original dataset announced via ProteomeXchange.

Title	SARS-Cov2 coronavirus spike protein-induced apoptosis, inflammatory and oxidative stress responses in THP-1-Like-Macrophages: potential role of angiotensin converting enzyme inhibitor (perindopril)
Description	A purified spike (S) glycoprotein for SARS-COV-2 coronavirus was used to studying its effects on THP-1 macrophages, PBMCs and HUVEC cells. The S protein mediates SARS-CoV-2 entry into cells through binding to angiotensin converting enzyme 2 (ACE2) receptors. We measured viability, intracellular cytokines release, oxidative stress, pro-inflammatory markers and THP-1-like macrophage polarization. We identified an increase in apoptosis, ROS generation, MCP-1 and intracellular calcium expression in THP-1 macrophages. Furthermore, stimulation with the S protein polarizes THP-1 macrophages towards pro-inflammatory futures with an increase in TNFα and MHC-II M1-like phenotype markers. Treatment of cells with an ACE inhibitor, perindopril at 100nM reduced apoptosis, ROS and MHC-II expression. We further analyzed the sensitivity of HUVEC cells after exposure to a conditioned media (CM) of THP-1 macrophages stimulated with S protein. CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, direct stimulation of HUVEC cells with S protein slightly increased HIF1α and MCP-1 expression which was significantly exaggerated by ACE inhibitor treatment. S protein stimulation induced ROS generation and changed mitogenic responses of PBMCs through upregulation of TNFα and IL-17 cytokine expressions. These effects were blunted by perindopril (100nM) treatment. Proteomic analysis of S protein stimulated THP-1 macrophages with or without perindopril (100nM) uncovered more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that blood and vascular component could be activated directly through S protein systemically present in circulation and that activation of local renin angiotensin system might be partially involved in this process.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:23.183.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bandar Alghanem
SpeciesList	scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: NCBITaxon:2697049; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-21 02:42:53	ID requested
1	2021-11-15 23:37:24	announced
⏵ 2	2023-11-14 08:52:23	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: SARS-CoV-2 Spike protein

Monocyte/macrophages

inflammation

angiotensin converting enzyme inhibitor

Proteomics

MOHAMED BOUDJELAL
contact affiliation	Medical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), NGHA, Riyadh 11426, Saudi Arabia
contact email	boudjelalmo@NGHA.MED.SA
lab head
Bandar Alghanem
contact affiliation	king abdullah international medical research center
contact email	ghanembandar@gmail.com
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/2021/11/PXD025516

PRIDE project URI

• PRIDE
  1. PXD025516
     1. Label: PRIDE project
     2. Name: SARS-Cov2 coronavirus spike protein-induced apoptosis, inflammatory and oxidative stress responses in THP-1-Like-Macrophages: potential role of angiotensin converting enzyme inhibitor (perindopril)