PXD012148

PXD012148 is an original dataset announced via ProteomeXchange.

Title	Glomerular filtrate proteins in acute cardiorenal syndrome
Description	Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Mechanistic investigations have focused on intrarenal cellular signaling induced by ischemia/reperfusion. Additional signals, “cardiorenal connectors”, have been postulated, but investigation in CRS-1 has been limited by a paucity of animal models and technical limitations precluding discovery studies of glomerular filtrate. To address these limitations we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR) and now report findings from a nanoscale mass spectrometry assay allowing proteomic exploration of Bowman’s space aspirate 2h after CA/CPR or sham procedure. Imaging, molecular weight and charge distribution, and minimal contribution of proteins from surrounding cell types confirmed the acquisition of filtrate. We detected filtration of low-molecular weight proteins specific to the heart following CA/CPR. Additional mass spectrometry performed on 24h urine collections from mice with deficient tubular endocytosis confirmed CA/CPR-specific cardiac protein filtration, and identified a novel, CA/CPR-specific, filtrate component: Cardiac LIM protein. Cardiac arrest-induced plasma release of Cardiac LIM protein occurred in mice and in critically-ill human cardiac arrest survivors and administration of recombinant cardiac LIM protein to mice altered renal function. Our findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2h after acute cardiovascular crisis. The presence and identification of cardiac-specific proteins in renal filtrate suggest a potential novel signaling mechanism in CRS-1. We expect these findings to advance understanding of cardiorenal syndrome.
HostingRepository	PRIDE
AnnounceDate	2019-02-27
AnnouncementXML	Submission_2019-03-06_01:20:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Piehowski
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-21 02:03:04	ID requested
1	2019-02-27 06:41:51	announced
⏵ 2	2019-03-06 01:20:18	announced	Updated publication reference for PubMed record(s): 30829647.

Wakasaki R, Matsushita K, Golgotiu K, Anderson S, Eiwaz MB, Orton DJ, Han SJ, Lee HT, Smith RD, Rodland KD, Piehowski PD, Hutchens MP, Glomerular filtrate proteins in acute cardiorenal syndrome. JCI Insight, 4(4):(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Kidney, glomerular filtrate, nanoproteomics, acute cardiorenal syndrome

Paul D. Piehowski
contact affiliation	Biological Sciences Division, Pacific Northwest National Laboratory
contact email	paul.piehowski@pnnl.gov
lab head
Paul Piehowski
contact affiliation	Pacific Northwest National Laboratory
contact email	paul.piehowski@pnnl.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012148
     1. Label: PRIDE project
     2. Name: Glomerular filtrate proteins in acute cardiorenal syndrome