Angiopoietin-1 requires oxidant signaling through p47phox to promote endothelial barrier defense

PloS One
Chandra C GhoshSamir M Parikh

Abstract

Reactive oxygen species (ROS) are largely considered to be pathogenic to normal endothelial function in disease states such as sepsis. We hypothesized that Angiopoietin-1 (Angpt-1), an endogenous agonist of the endothelial-specific receptor, Tie-2, promotes barrier defense by activating NADPH oxidase (NOX) signaling. Using primary human microvascular endothelial cells (HMVECs), we found that Angpt-1 stimulation induces phosphorylation of p47phox and a brief oxidative burst that is lost when chemical inhibitors of NOX activity or siRNA against the NOX component p47phox were applied. As a result, there was attenuated ROS activity, disrupted junctional contacts, enhanced actin stress fiber accumulation, and induced gap formation between confluent HMVECs. All of these changes were associated with weakened barrier function. The ability of Angpt-1 to prevent identical changes induced by inflammatory permeability mediators, thrombin and lipopolysaccharides (LPS), was abrogated by p47phox knockdown. P47phox was required for Angpt-1 to activate Rac1 and inhibit mediator-induced activation of the small GTPase RhoA. Finally, Angpt-1 gene transfer prevented vascular leakage in wildtype mice exposed to systemically administered LPS, but not...Continue Reading

References

Sep 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C TiruppathiI Giaever
Dec 9, 1993·Nature·I Giaever, C R Keese
Oct 7, 1997·Circulation Research·A L WongK G Peters
Oct 16, 1999·Circulation Research·C Kunsch, R M Medford
Mar 31, 2000·Nature Medicine·G ThurstonG D Yancopoulos
Sep 25, 2001·Journal of Applied Physiology·S M Dudek, J G Garcia
Apr 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Carolyn R HoyalBernard M Babior
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Mark S WainwrightD Martin Watterson
Dec 6, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Md Ruhul AbidWilliam C Aird
Nov 17, 2004·Molecular and Cellular Biochemistry·Masuko Ushio-Fukai, R Wayne Alexander
Dec 22, 2004·Circulation·Bernhard WitzenbichlerCarsten Tschope
Jul 29, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rania HarfoucheSabah N A Hussain
Dec 24, 2005·Physiological Reviews·Dolly Mehta, Asrar B Malik
Apr 11, 2006·Biochemical and Biophysical Research Communications·Claudia StielowHenning Morawietz
Jun 17, 2006·Cancer Research·Young Mee KimKong-Joo Lee
Aug 24, 2006·Science's STKE : Signal Transduction Knowledge Environment·Masuko Ushio-Fukai
Oct 20, 2006·The New England Journal of Medicine·James A Russell
Jun 15, 2007·The Journal of Biological Chemistry·Tadanori MammotoVikas P Sukhatme
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Jul 29, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Weiguo ChenJeffrey R Jacobson
Feb 28, 2009·Biochemical and Biophysical Research Communications·Jeong-Ah HwangChung-Hyun Cho
Oct 9, 2009·Kidney International·Duk Hoon KimWon Kim
Mar 23, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sascha DavidSamir M Parikh
Sep 2, 2011·The Journal of Clinical Investigation·Mei TranSamir M Parikh
Sep 3, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Sascha DavidSamir M Parikh
Nov 2, 2011·Critical Care : the Official Journal of the Critical Care Forum·Philipp KumpersNelli Shushakova
Jun 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Chandra C GhoshSamir M Parikh
Aug 15, 2012·Critical Care Medicine·Sascha DavidSamir M Parikh
Jun 26, 2013·Methods in Enzymology·Nataliya M MishinaVsevolod V Belousov
May 3, 2014·American Journal of Respiratory and Critical Care Medicine·Zhihui XieKirk M Druey
Oct 22, 2014·Nature Communications·Yulia G ErmakovaVsevolod V Belousov

❮ Previous
Next ❯

Citations

Mar 5, 2016·In Vitro Cellular & Developmental Biology. Animal·Wenzhen ZhuGuorong Li
Jan 31, 2017·The Journal of Allergy and Clinical Immunology·Vladislav A LitoshMarc E Rothenberg
Mar 25, 2017·Free Radical Biology & Medicine·Katrin SchröderRalf P Brandes
May 4, 2017·Journal of the American Society of Nephrology : JASN·Samir M Parikh
Jun 6, 2017·Current Opinion in Hematology·Samir M Parikh
Oct 13, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ramin RokhzanRamaswamy Krishnan

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
transfection
biosensor
GLISA
pulldown

Software Mentioned

ImageJ
GraphPadPrism5
Adobe Photoshop

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Related Papers

American Journal of Physiology. Lung Cellular and Molecular Physiology
Sascha DavidSamir M Parikh
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Rania HarfoucheSabah N A Hussain
© 2021 Meta ULC. All rights reserved