Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells

Abstract Despite Paraquat (PQ) being banned in several countries, it is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human and animal brain cells by generating Reactive Oxygen Species (ROS). However, there is few evidence of PQ e...

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Autores principales:	Vujić Tatjana, Schvartz Domitille, Sanchez Jean-Charles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/084e55285876488aafdac7ec4a55a5eb
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spelling	oai:doaj.org-article:084e55285876488aafdac7ec4a55a5eb2021-12-02T18:02:31ZParaquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells10.1038/s41598-021-97175-w2045-2322https://doaj.org/article/084e55285876488aafdac7ec4a55a5eb2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97175-whttps://doaj.org/toc/2045-2322Abstract Despite Paraquat (PQ) being banned in several countries, it is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human and animal brain cells by generating Reactive Oxygen Species (ROS). However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), one of the major component of the Blood–Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposure of 1, 10 and 100 µM of PQ for 24 h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level were performed to verify proteomics results. A total of 3753 proteins were quantified out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins, confirming the well-known mechanism of PQ inducing oxidative stress. Additionally, this study also described the cholesterol biosynthesis modulation on HBMECs not yet described. In conclusion, our data indicate the toxic effect of PQ on HBMECs by downregulating proteins involved in mitochondrial complex I and cholesterol pathways.Vujić TatjanaSchvartz DomitilleSanchez Jean-CharlesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vujić Tatjana Schvartz Domitille Sanchez Jean-Charles Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
description	Abstract Despite Paraquat (PQ) being banned in several countries, it is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human and animal brain cells by generating Reactive Oxygen Species (ROS). However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), one of the major component of the Blood–Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposure of 1, 10 and 100 µM of PQ for 24 h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level were performed to verify proteomics results. A total of 3753 proteins were quantified out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins, confirming the well-known mechanism of PQ inducing oxidative stress. Additionally, this study also described the cholesterol biosynthesis modulation on HBMECs not yet described. In conclusion, our data indicate the toxic effect of PQ on HBMECs by downregulating proteins involved in mitochondrial complex I and cholesterol pathways.
format	article
author	Vujić Tatjana Schvartz Domitille Sanchez Jean-Charles
author_facet	Vujić Tatjana Schvartz Domitille Sanchez Jean-Charles
author_sort	Vujić Tatjana
title	Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
title_short	Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
title_full	Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
title_fullStr	Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
title_full_unstemmed	Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
title_sort	paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/084e55285876488aafdac7ec4a55a5eb
work_keys_str_mv	AT vujictatjana paraquatinducedcholesterolbiosynthesisproteinsdysregulationinhumanbrainmicrovascularendothelialcells AT schvartzdomitille paraquatinducedcholesterolbiosynthesisproteinsdysregulationinhumanbrainmicrovascularendothelialcells AT sanchezjeancharles paraquatinducedcholesterolbiosynthesisproteinsdysregulationinhumanbrainmicrovascularendothelialcells
_version_	1718378849875525632

Paraquat-induced cholesterol biosynthesis proteins dysregulation in human brain microvascular endothelial cells

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