PXD001107

PXD001107 is an original dataset announced via ProteomeXchange.

Title	Detection of Dichlorvos Aducts in Hepatocyte Cell Line LC-MS/MS
Description	Toxicity of dichlorvos (DDVP), an organophosphate (OP) pesticide, classically results from modification of the serine in the active sites of cholinesterases. However, DDVP also forms adducts on unrelated targets such as transferrin and albumin, suggesting that DDVP causes cellular perturbation by modifying non-cholinesterase targets. Here, we identify novel DDVP-modified targets in lysates of a human hepatocyte-like cell line (HepaRG) using a direct LC-MS assay of DDVP exposed lysates or using a competitive pull-down experiments with a biotin-linked organophosphorus compound (10-fluoroethoxyphosphinyl-N-biotinamidopentyldecanamide; FP-biotin), which competes with DDVP for similar binding sites. Using these strategies, we show that DDVP forms adduct to several proteins important to the cellular metabolic pathways and cellular differentiation, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and actin. We validated the results using purified proteins and enzymatic assays. The study not only identified novel DDVP-modified targets but also suggested that the modification directly inhibits the enzymes. The current approach provides information for future hypothesis studies to understand the underlying mechanism of toxicity of DDVP in non-neuronal tissues.
HostingRepository	PRIDE
AnnounceDate	2014-10-23
AnnouncementXML	Submission_2014-10-23_03:58:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	William Dennis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2014-07-03 03:21:33	ID requested
1	2014-07-31 04:45:04	announced
⏵ 2	2014-10-23 03:58:08	announced	Updated project metadata.

Bui-Nguyen TM, Dennis WE, Jackson DA, Stallings JD, Lewis JA, Detection of dichlorvos adducts in a hepatocyte cell line. J Proteome Res, 13(8):3583-95(2014) [pubmed]

curator keyword: Biomedical

submitter keyword: Dichorvos, Hepatocyte Cell line, LC-MS/MS

John A Lewis
contact affiliation	USACEHR
contact email	john.a.lewis5.civ@mail.mil
lab head
William Dennis
contact affiliation	USACEHR
contact email	William.e.dennis.civ@mail.mil
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/2014/07/PXD001107

PRIDE project URI

• PRIDE
  1. PXD001107
     1. Label: PRIDE project
     2. Name: Detection of Dichlorvos Aducts in Hepatocyte Cell Line LC-MS/MS