PXD003811

PXD003811 is an original dataset announced via ProteomeXchange.

Title	SILAC-Based Proteomics of Primary Human Kidney Cells treated with Sex Hormones.
Description	Male sex predispose to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within kidney, we hypothesized that dihydrotestosterone (DHT) would impair the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT- and 17β-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC), in 4 different experiments. Of the 5043 quantified proteins, 76 were differentially regulated. Biological processes related to energy metabolism were significantly enriched among DHT-regulated proteins. SILAC ratios of 3 candidates representing glycolysis, N-acetylglucosamine metabolism and fatty acid β-oxidation, namely glucose-6-phosphate isomerase (GPI), glucosamine-6-phosphate-N-acetyltransferase 1 (GNPNAT1) and mitochondrial trifunctional protein subunit alpha (HADHA), were verified in vitro. In vivo, renal GPI and HADHA protein expression was increased in males. Furthermore, male sex was associated to higher GPI, GNPNAT1 and HADHA protein expression in diabetic Akita mice. Functional group enrichment analysis revealed a link between our DHT-regulated proteins and glycosphingolipid metabolism within the male kidney. This is the most in depth quantitative proteomic study of human primary PTEC response to sex hormone treatment. In this study we open new perspectives on how to explore the molecular mechanisms responsible for the deleterious effects of androgens in the context of kidney disease, especially diabetic nephropathy.
HostingRepository	PRIDE
AnnounceDate	2017-01-17
AnnouncementXML	Submission_2017-01-17_11:44:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergi Clotet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-03-18 01:34:58	ID requested
⏵ 1	2017-01-17 11:44:27	announced

Clotet S, Soler MJ, Riera M, Pascual J, Fang F, Zhou J, Batruch I, Vasiliou SK, Dimitromanolakis A, Barrios C, Diamandis EP, Scholey JW, Konvalinka A, Stable Isotope Labeling with Amino Acids (SILAC)-Based Proteomics of Primary Human Kidney Cells Reveals a Novel Link between Male Sex Hormones and Impaired Energy Metabolism in Diabetic Kidney Disease. Mol Cell Proteomics, 16(3):368-385(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Kidney cells, Sex hormones, SILAC, Proteomics

Ana Konvalinka
contact affiliation	Toronto General Hospital, University of Toronto, Toronto, Canada
contact email	ana.konvalinka@mail.utoronto.ca
lab head
Sergi Clotet
contact affiliation	Toronto General Hospital
contact email	sclotet88@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/2017/01/PXD003811

PRIDE project URI

• PRIDE
  1. PXD003811
     1. Label: PRIDE project
     2. Name: SILAC-Based Proteomics of Primary Human Kidney Cells treated with Sex Hormones.