Nascent Proteomes in Peripheral Blood Mononuclear Cells as a Novel Source for Biomarker Discovery in Human Stroke

• Type of Material: Article
• Authors: Fang Bian, Morehouse School of Medicine; Roger Simon, Emory University; Yun Li, Morehouse School of Medicine; Larry David, Oregon Health Science University; Jolita Wainwright, Morehouse School of Medicine; Casey L. Hall, Emory University; Michael Frankel, Emory University; An Zhou, Morehouse School of Medicine
• Language: English
• Date: 2014-04-01
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/STROKEAHA.113.004576
• Title of Journal or Parent Work: Stroke
• ISSN: 0039-2499
• Volume: 45
• Issue: 4
• Start Page: 1177
• End Page: 1179
• Grant/Funding Information: This study was supported by grants from National Institute of Health: U54 NS060659 (NINDS, Neuroscience Institute, MSM); 1R21NS075538 (AZ); C06 RR-07571 (NCRR, MSM); R25NS065739 (CLH); National Institute of Minority Health and Health Disparities: G12 RR003034 (MSM); MSM Endowment (RPS).
• Keywords: proteomics; stroke; Cardiovascular System & Cardiology; leukocytes; Neurosciences & Neurology; biomarkers; ISCHEMIC-STROKE; Clinical Neurology; Peripheral Vascular Disease; Science & Technology; Life Sciences & Biomedicine; GENE-EXPRESSION
• Research Categories: Biology, Neuroscience; Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

BACKGROUND AND PURPOSE - : The proteome of newly synthesized proteins (nascent proteome) in peripheral blood mononuclear cells (PBMCs) can be a novel source of stroke biomarkers. Changes in the PBMC nascent proteome after stroke reflect the dynamic response-in-action not detectable in the total proteome (all existing proteins) in blood. Here, we test the application of nascent proteomics as a novel approach for stroke biomarker discovery. METHODS - : The PBMC nascent proteome in human blood was determined by metabolic labeling of fresh PBMC cultures with azidohomoalanine (an azide-containing methionine surrogate), followed by mass spectrometry detection and quantification of azidohomoalanine-labeled proteins. The PBMC nascent and total proteomes were compared between patients with stroke and matched controls. RESULTS - : Both PBMC nascent and total proteomes showed differences between stroke patients and controls. Results of hierarchical clustering analysis of proteomic data revealed greater changes in the nascent than in the total PBMC proteomes, supporting the usefulness of the PBMC nascent proteome as a novel source of stroke biomarkers. CONCLUSIONS - : Nascent proteomes in PBMC can be a novel source for biomarker discovery in human stroke.