PXD034257

PXD034257 is an original dataset announced via ProteomeXchange.

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

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.

10.1080/15376516.2022.2156005;

submitter keyword: Drug-induced liver injury

Data-independent Acquisition

Clozapine

Proteomics

Systems ToxicologyDrug-induced liver injury

Data-independent Acquisition

Clozapine

Proteomics

Systems Toxicology

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/12/PXD034257

PRIDE project URI

• PRIDE
  1. PXD034257
     1. Label: PRIDE project
     2. Name: Toxicoproteomics reveals an effect of Clozapine on autophagy in human liver spheroids