PXD034257 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids |
Description | Clozapine 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:41:23.041.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Bjoern Titz |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-06-01 11:21:18 | ID requested | |
1 | 2022-12-09 08:45:32 | announced | |
2 | 2023-11-14 08:56:35 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 05:41:23 | announced | 2024-10-22: Updated project metadata. |
Publication List
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 affiliation | Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchatel, Switzerland |
contact email | bjorn.titz@pmi.com |
lab head | |
Bjoern Titz |
contact affiliation | Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland |
contact email | bjorn.titz@pmi.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD034257
- Label: PRIDE project
- Name: Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids