Pharmaceutical Sciences Faculty Publications

Quantitative Proteomic Analysis of Sokotrasterol Sulfate-Stimulated Primary Human Endothelial Cells

Document Type

Article

Publication Date

2-1-2005

Journal Title

Molecular & Cellular Proteomics

ISSN

1535-9476

Volume

4

Issue

2

First Page

191

Last Page

204

DOI

10.1074/mcp.M400152-MCP200

PubMed ID

15611527

Abstract

The endothelium forms a continuous monolayer at the interface between blood and tissue and contributes significantly to the sensing and transducing of signals between blood and tissue. New blood vessel formation, or angiogenesis, is initiated by the activation of endothelial cells and is an important process required for various pathological and physiological situations. This study used cleavable isotope-coded affinity tag reagents combined with mass spectrometry to investigate the molecular basis of a recently discovered angiogenesis-promoting steroid, sokotrasterol sulfate. Changes in the relative abundances of over 1000 proteins within human endothelial cells treated with sokotrasterol sulfate and vehicle-treated cells were identified and quantitated using this technique. A method that examines the entire ensemble of quantitative measurements was developed to identify proteins that showed a statistically significant change in relative abundance resulting from treatment with sokotrasterol sulfate. A total of 93 proteins was significantly up-regulated, and 37 were down-regulated in response to sokotrasterol sulfate stimulation of endothelial cells. Among the up-regulated proteins, several were identified that are novel to endothelial cells and are likely involved in cell communication and morphogenesis. These findings are consistent with a role for sokotrasterol sulfate in endothelial sprouting.

Keywords

Cations, cells, cultured, cholestenes, chromatography, ion exchange, chromatography, liquid, down-regulation, endothelial cells, endothelium, vascular, immunoblotting, mass spectrometry, neovascularization, pathologic, peptides, proteomics, signal transduction, umbilical veins

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