PXD050155-2

PXD050155 is an original dataset announced via ProteomeXchange.

Title	Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis
Description	Cell death is a fundamental process for health and disease. Emerging research unveiled numerous distinct cell death modalities with similar and intertwined signaling pathways, but different outcomes, rising the need to understand the decision points during cell death signaling. Paracetamol (Acetaminophen, APAP)-induced hepatocyte death includes several apoptotic processes, but eventually ends as oncotic necrosis without any caspase activation. Here, we studied this paradoxical form of cell death and revealed that APAP not only fails to activate caspases, but also strongly impedes their activation upon classical apoptosis induction. We explored different hypotheses and deciphered that high oxidative stress consistently blocks caspase activity. Importantly, caspase inhibition and the associated switch from apoptotic to necrotic cell death is reversible through the administration of antioxidants. Thus, exemplified by APAP-induced cell death, our study stresses that the cellular redox status is a critical decision maker between different forms of cell death as it directly affects caspase activity.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:59:33.961.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	dihydroxylated residue; S-nitrosyl-L-cysteine; monohydroxylated residue; L-cysteic acid (L-cysteine sulfonic acid); L-cysteine glutathione disulfide
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-26 09:04:21	ID requested
1	2024-09-24 05:41:17	announced
⏵ 2	2024-10-22 06:59:34	announced	2024-10-22: Updated project metadata.

Lambrecht R, Jansen J, Rudolf F, El-Mesery M, Caporali S, Amelio I, Stengel F, Brunner T, Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis. Cell Death Dis, 15(9):659(2024) [pubmed]

10.1038/s41419-024-06998-8;

submitter keyword: glutathione,Paracetamol/APAP, necrosis, oxidative stress, apoptosis, caspases

Prof. Dr. Florian Stengel
contact affiliation	Department of Biology, Universitätsstraße 10, 78457 Konstanz, Germany
contact email	florian.stengel@uni.kn
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050155
     1. Label: PRIDE project
     2. Name: Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis