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)

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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:Zanivan, Dr Sara Rossana and Blyth, Dr Karen and Anderson, Professor Kurt and Patella, Dr Francesca and Ryan, Professor Kevin and Neilson, Ms Lisa and Athineos, Mr Dimitris and Erami Rud Majani, Mrs Zahra
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 > Institute 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

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