Dataset Information

Proteomics analysis unraveled paraquat-induced cholesterol biosynthesis dysregulation in human brain microvascular endothelial cells

ABSTRACT: Despite its banishment in several countries, Paraquat (PQ) is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human or animal brain cells such as glial cells or neurons through biological processes as redox by generation of Reactive Oxygen Species (ROS). This specific perturbation has already proven its association for increasing the risk of developing a long-term brain impairment in in vitro and in vivo studies using brain cells. However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), a particular cell type acting as a macromolecule permeability regulator in the Blood-Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposition of 1, 10 and 100 µM of PQ for 24h 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 of PQ-treated HBMECs were performed to verify proteomics results. Proteomic experiment reported a total of 3753 quantified proteins out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed that the modified proteins are involved in pathways such as the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins. This study also unveiled the modulation of the cholesterol metabolism. In conclusion, most of the highly differentially expressed proteins (DEPs) in PQ-treated HBMECs were associated to the ubiquinone metabolism pathway confirming the well know mechanism of PQ inducing oxidative stress and inhibit mitochondrial complex I activity. Additionally, this study also described the cholesterol biosynthesis modulation on primary human brain endothelial cells not yet described.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain Microvascular Endothelial Cell

SUBMITTER: Tatjana Vujic

LAB HEAD: Jean-Charles Sanchez

PROVIDER: PXD026975 | Pride | 2022-02-17

REPOSITORIES: Pride

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

Tatjana Vujić V Domitille Schvartz S Jean-Charles Sanchez S

Scientific reports 20210913 1

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 exposur ...[more]

PMID: 34518572

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