PXD038016

PXD038016 is an original dataset announced via ProteomeXchange.

Title	Characterization of complement C3 as a marker of alpha-amanitin toxicity by comparative secretome profiling
Description	In the human body, proteins secreted into peripheral blood vessels are known as the secretome, and they represent the physiological or pathological status of cells. The unique response of cells to toxin exposure can be confirmed via secretome analysis, which can be used to discover toxic mechanisms or exposure markers. Alpha-amanitin (-AMA) is the most widely studied amatoxin and inhibits transcription and protein synthesis by directly interacting with RNA polymerase II. However, secretory proteins released during hepatic failure caused by -AMA have not been fully characterized. In this study, we analyzed secretome of -AMA-treated Huh-7 cells and mice using a comparative proteomics technique. Overall, 1,505 and 1,440 proteins were identified and quantified, respectively. Among them, 4 and 127 proteins were significantly upregulated and downregulated, respectively. Based on the bioinformatics results for the significantly downregulated proteins, we identified complement component 3 (C3) as a marker for -AMA-induced hepatotoxicity. Through western blot and C3 ELISA assays, we validated -AMA-induced downregulation of C3. In conclusion, using comparative proteomics and molecular biology techniques, we found that -AMA-induced hepatotoxicity reduced C3 levels in the secretome. We expect that this study will aid in identifying new toxic mechanisms, therapeutic targets, and exposure markers of -AMA-induced hepatotoxicity.
HostingRepository	PRIDE
AnnounceDate	2024-05-23
AnnouncementXML	Submission_2024-05-23_00:02:05.432.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Doeun Kim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-07 10:08:11	ID requested
⏵ 1	2024-05-23 00:02:06	announced

Kim D, Lee MS, Sim H, Lee S, Lee HS, Characterization of complement C3 as a marker of alpha-amanitin toxicity by comparative secretome profiling. Toxicol Res, 39(2):251-262(2023) [pubmed]

10.1007/s43188-022-00163-z;

submitter keyword: alpha-amanitin

toxic mushroom

secretomes

exposure marker

Complement component 3

Sangkyu Lee
contact affiliation	BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
contact email	sangkyu@knu.ac.kr
lab head
Doeun Kim
contact affiliation	College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
contact email	kdkdl1230@gmail.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/2024/05/PXD038016

PRIDE project URI

• PRIDE
  1. PXD038016
     1. Label: PRIDE project
     2. Name: Characterization of complement C3 as a marker of alpha-amanitin toxicity by comparative secretome profiling