PXD038516

PXD038516 is an original dataset announced via ProteomeXchange.

Title	Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells
Description	Morphine, a commonly used antinociceptive drug in hospitals, is known to cross the blood-brain barrier (BBB) by first passing through brain endothelial cells. Despite its pain-relieving effect, morphine also has detrimental effects, such as the potential induction of redox imbalance in the brain. However, there is still insufficient evidence of these effects on the brain, particularly on the brain endothelial cells and the extracellular vesicles that they naturally release. Indeed, extracellular vesicles (EVs) are nanosized bioparticles produced by almost all cell types and are currently thought to reflect the physiological state of their parent cells. These vesicles have emerged as a promising source of biomarkers by indicating the functional or dys-functional state of their parent cells and, thus, allowing a better understanding of the biological processes involved in an adverse state. However, there is very little information on the mor-phine effect on human brain microvascular endothelial cells (HBMECs), and even less on their released EVs. Therefore, the current study aimed at unraveling the detrimental mechanisms of morphine exposure (at 1, 10, 25, 50 and 100 µM) for 24 h on human brain microvascular endothe-lial cells as well as on their associated EVs. Isolation of EVs was carried out using an affini-ty-based method. Several orthogonal techniques (NTA, western blotting and proteomics analy-sis) were used to validate the EVs enrichment, quality and concentration. Data-independent mass spectrometry (DIA-MS)-based proteomics was applied in order to analyze the proteome modu-lations induced by morphine on HBMECs and EVs. We were able to quantify almost 5500 pro-teins in HBMECs and 1500 proteins in EVs, of which 256 and 148, respectively, were found to be differentially expressed in at least one condition. Pathway enrichment analysis revealed that the “cell adhesion and extracellular matrix remodeling” process and the “HIF1 pathway”, a pathway related to oxidative stress responses, were significantly modulated upon morphine exposure in HBMECs and EVs. Altogether, the combination of proteomics and bioinformatics findings high-lighted shared pathways between HBMECs exposed to morphine and their released EVs. These results put forward molecular signatures of morphine-induced toxicity in HBMECs that were also carried by EVs. Therefore, EVs could potentially be regarded as a useful tool to investigate brain endothelial cells dysfunction, and to a different extent, the BBB dysfunction in patient cir-culation using these “signature pathways”.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:02.167.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tatjana Vujic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetic acid derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-02 06:36:41	ID requested
1	2023-03-11 11:56:36	announced
⏵ 2	2023-11-14 08:44:10	announced	2023-11-14: Updated project metadata.

Vuji, ć T, Schvartz D, Furlani IL, Meister I, Gonz, á, lez-Ruiz V, Rudaz S, Sanchez JC, Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells. Cells, 11(23):(2022) [pubmed]

submitter keyword: extracellular vesicles

endothelial cells

morphine

CNS

BBB

proteomics

DIA-MS

oxidative stress

HIF-1

cell adhesion

extracellular matrix remodeling

Jean-Charles Sanchez
contact affiliation	Department of Medicine, University of Geneva,1211 Geneva, Switzerland
contact email	jean-charles.sanchez@unige.ch
lab head
Tatjana Vujic
contact affiliation	Department of Medicine, University of Geneva, Geneva, Switzerland
contact email	tatjana.vujic@unige.ch
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/2023/03/PXD038516

PRIDE project URI

• PRIDE
  1. PXD038516
     1. Label: PRIDE project
     2. Name: Oxidative Stress and Extracellular Matrix Remodeling Are Signature Pathways of Extracellular Vesicles Released upon Morphine Exposure on Human Brain Microvascular Endothelial Cells