Ubiquinone Metabolism and Transcription HIF-1 Targets Pathway Are Toxicity Signature Pathways Present in Extracellular Vesicles of Paraquat-Exposed Human Brain Microvascular Endothelial Cells.
BBB
CNS
DIA-MS
HIF-1
endothelial cells
extracellular vesicles
hypoxia
oxidative stress
paraquat
proteomics
ubiquinone metabolism
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
11 May 2021
11 May 2021
Historique:
received:
20
04
2021
revised:
03
05
2021
accepted:
08
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
10
6
2021
Statut:
epublish
Résumé
Over the last decade, the knowledge in extracellular vesicles (EVs) biogenesis and modulation has increasingly grown. As their content reflects the physiological state of their donor cells, these "intercellular messengers" progressively became a potential source of biomarker reflecting the host cell state. However, little is known about EVs released from the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze their EVs proteome modulation after paraquat (PQ) stimulation, a widely used herbicide known for its neurotoxic effect. Size distribution, concentration and presence of well-known EV markers were assessed. Identification and quantification of PQ-exposed EV proteins was conducted by data-independent acquisition mass spectrometry (DIA-MS). Signature pathways of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results highlighted that EVs exposed to PQ have modulated pathways, namely the ubiquinone metabolism and the transcription HIF-1 targets. These pathways may be potential molecular signatures of the PQ-induced toxicity carried by EVs that are reflecting their cell of origin by transporting with them irreversible functional changes.
Identifiants
pubmed: 34064677
pii: ijms22105065
doi: 10.3390/ijms22105065
pmc: PMC8150401
pii:
doi:
Substances chimiques
Biomarkers
0
HIF1A protein, human
0
Herbicides
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Proteome
0
Ubiquinone
1339-63-5
Paraquat
PLG39H7695
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R43 AG063589
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA239845
Pays : United States
Organisme : Swiss Centre for Applied Human Toxicology
ID : 313926
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