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PXD002235

PXD002235 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleComparative proteomic analysis of human liver tissue and isolated hepatocytes with a focus on proteins determining drug exposure
DescriptionFreshly isolated human hepatocytes are considered the gold standard for in vitro studies of liver functions, including drug transport, metabolism, and toxicity. For accurate predictions of in vivo outcome, the isolated hepatocytes should reflect the phenotype of their in vivo counterpart, i.e., hepatocytes in human liver tissue. Here, we quantified and compared the membrane proteomes of freshly isolated hepatocytes and human liver tissue using a label-free shotgun proteomics approach. A total of 5144 unique proteins were identified, spanning over six orders of magnitude in abundance. There was a good global correlation in protein abundance. However, the expression of many plasma membrane proteins was lower in the isolated hepatocytes than in the liver tissue. This included transport proteins that determine hepatocyte exposure to many drugs and endogenous compounds. Pathway analysis of the differentially expressed proteins confirmed that hepatocytes are exposed to oxidative stress during isolation and suggested that plasma membrane proteins were degraded via the protein ubiquitination pathway. Finally, using pitavastatin as an example, we show how protein quantifications can improve in vitro predictions of in vivo liver clearance. We tentatively conclude that our data set will be a useful source for improved hepatocyte predictions of in vivo outcome.
HostingRepositoryPRIDE
AnnounceDate2015-07-17
AnnouncementXMLSubmission_2015-07-20_05:31:26.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJacek Wisniewski
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-05-27 00:22:25ID requested
12015-07-16 19:31:56announced
22015-07-20 05:31:27announcedUpdated publication reference for PubMed record(s): 26167961.
Publication List
Vildhede A, Wi, ś, niewski JR, Nor, é, n A, Karlgren M, Artursson P, Comparative Proteomic Analysis of Human Liver Tissue and Isolated Hepatocytes with a Focus on Proteins Determining Drug Exposure. J Proteome Res, 14(8):3305-14(2015) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: Human liver, human hepatocyte, FASP, ADME proteins
Contact List
Jacek R Wisniewski
contact affiliationMax Planck Institute of Biochemistry, Martinsried, Germany
contact emailjwisniew@biochem.mpg.de
lab head
Jacek Wisniewski
contact affiliationProteomics
contact emailjwisniew@biochem.mpg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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