In-depth proteomics identifies a role for autophagy in controlling reactive oxygen species mediated endothelial permeability

Patella, F., Neilson, L., Athineos, D., Erami Rud Majani, Z., Anderson, K. I., Blyth, K. , Ryan, K. and Zanivan, S. R. (2016) In-depth proteomics identifies a role for autophagy in controlling reactive oxygen species mediated endothelial permeability. Journal of Proteome Research, 15(7), pp. 2187-2197. (doi: 10.1021/acs.jproteome.6b00166) (PMID:27246970)

Abstract

Endothelial cells (ECs) form the inner layer of blood vessels and physically separate the blood from the surrounding tissue. To support tissues with nutrients and oxygen, the endothelial monolayer is semipermeable. When EC permeability is altered, blood vessels are not functional, and this is associated with disease. A comprehensive knowledge of the mechanisms regulating EC permeability is key in developing strategies to target this mechanism in pathologies. Here we have used an in vitro model of human umbilical vein endothelial cells mimicking the formation of a physiologically permeable vessel and performed time-resolved in-depth molecular profiling using stable isotope labeling by amino acids in cell culture mass spectrometry (MS)-proteomics. Autophagy is induced when ECs are assembled into a physiologically permeable monolayer. By using siRNA and drug treatment to block autophagy in combination with functional assays and MS proteomics, we show that ECs require autophagy flux to maintain intracellular reactive oxygen species levels, and this is required to maintain the physiological permeability of the cells.

• Item Type: Articles
• Additional Information: This work was funded by Cancer Research UK (Grant No. C596/A12935 (S.Z.) and C596/A17196 (core)).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Blyth, Professor Karen and Anderson, Professor Kurt and Ryan, Professor Kevin and Neilson, Ms Lisa and Erami Rud Majani, Mrs Zahra and Zanivan, Professor Sara and Patella, Dr Francesca and Athineos, Mr Dimitris
• Authors: Patella, F., Neilson, L., Athineos, D., Erami Rud Majani, Z., Anderson, K. I., Blyth, K., Ryan, K., and Zanivan, S. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Proteome Research
• Publisher: American Chemical Society
• ISSN: 1535-3893
• ISSN (Online): 1535-3907
• Copyright Holders: Copyright © 2016 American Chemical Society
• First Published: First published in Journal of Proteome Research 15(7): 2187-2197
• Publisher Policy: Reproduced in accordance with the publisher copyright policy