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PXD034257

PXD034257 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleToxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids
DescriptionClozapine is an atypical antipsychotic drug for treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude a more common use as a first-line therapy of schizophrenia. Toxicoproteomics approaches have been demonstrated to effectively guide the identification of toxicological mechanisms. Here, to further our understanding of Clozapine's molecular effects we performed a Data-independent Acquisition (DIA)-based quantitative proteomics investigation of Clozapine-treated human liver spheroid cultures. In total, we quantified 4,479 proteins across five treatment groups (vehicle, 15 µM, 30 µM, 60 µM Clozapine, and 10 ng/mL TNFa + IL-1a). 60 µM Clozapine treatment yielded 36 differentially expressed proteins (fdr < 0.05). Gene-set enrichment analysis indicated perturbation of several gene-sets, which included interferon gamma signaling (e.g., IFNGR1) and prominently autophagy related processes (e.g., upregulation of SQSTM1, MAP1LC3B/LC3B2, GABARAPL2, and NCOA4). Clozapine's effects on autophagy were confirmed using conventional SQSTM1 and LC3B markers by targeted mass-spectrometry and Western Blot.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:41:23.041.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBjoern Titz
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-01 11:21:18ID requested
12022-12-09 08:45:32announced
22023-11-14 08:56:35announced2023-11-14: Updated project metadata.
32024-10-22 05:41:23announced2024-10-22: Updated project metadata.
Publication List
10.1080/15376516.2022.2156005;
Keyword List
submitter keyword: Drug-induced liver injury
Data-independent Acquisition
Clozapine
Proteomics
Systems ToxicologyDrug-induced liver injury
Data-independent Acquisition
Clozapine
Proteomics
Systems Toxicology
Contact List
Bjoern Titz
contact affiliationPhilip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchatel, Switzerland
contact emailbjorn.titz@pmi.com
lab head
Bjoern Titz
contact affiliationPhilip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
contact emailbjorn.titz@pmi.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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