PXD067007-1

PXD067007 is an original dataset announced via ProteomeXchange.

Title	An environmentally relevant mixture of organophosphate esters induces cholesterol biosynthesis in THP-1 macrophages
Description	Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, are environmental toxicants known to disrupt lipid metabolism. Although most studies have focused on individual OPEs, environmental exposures typically involve complex mixtures. Our previous studies demonstrated that a representative OPE mixture from Canadian household dust promotes cholesterol and lipid droplet accumulation in THP-1 macrophages. However, the molecular mechanisms underlying this lipid dysregulation remain unclear. Here, we employed tandem mass tag (TMT)-based quantitative proteomics to investigate how OPE mixtures alter protein expression and lipid regulation in macrophages. THP-1 macrophages were exposed to vehicle or environmentally relevant dilutions (1:100,000 and 1:20,000) of the OPE mixture for 48 hours. Lysates were subjected to TMT labeling and mass spectrometry. Bioinformatic analyses using STRING and Ingenuity Pathway Analysis identified 162 differentially expressed proteins, with unsupervised clustering highlighting cholesterol biosynthesis as a key pathway. Further validation via qPCR and upstream analysis implicated the sterol regulatory element-binding protein 2 (SREBP2) signaling axis in OPE-induced cholesterol biosynthesis. Functional assays revealed that co-treatment with atorvastatin, an HMG-CoA reductase inhibitor, prevented cholesterol accumulation and mitigated lipid droplet formation. These findings provide the first evidence that an environmentally relevant OPE mixture can induce cholesterol biosynthesis in human macrophages.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:33:52.507.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Koren Mann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-06 12:13:15	ID requested
⏵ 1	2026-05-24 16:33:53	announced

Giles BH, Robaire B, Mann KK, An environmentally relevant mixture of organophosphate esters induces cholesterol biosynthesis in THP-1 macrophages. Toxicol Sci, 209(5):(2026) [pubmed]

10.1093/toxsci/kfag048;

submitter keyword: macrophage, Flame retardants,Organophosphate esters, mixture, lipid droplets, cholesterol biosynthesis, Proteomics

Koren Mann
contact affiliation	McGill University
contact email	koren.mann@mcgill.ca
lab head
Koren Mann
contact affiliation	McGill University
contact email	koren.mann@mcgill.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067007
     1. Label: PRIDE project
     2. Name: An environmentally relevant mixture of organophosphate esters induces cholesterol biosynthesis in THP-1 macrophages