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Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release.

Agouni, Abdelali, Mostefai, HA, Porro, C, Carusio, N, Favre, J, Richard, V, Henrion, D, Martínez, MC and Andriantsitohaina, R (2007) Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. The FASEB Journal, 21 (11). pp. 2735-2741.

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Abstract

Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation. Among the candidate proteins harbored by MPs, we recently showed that sonic hedgehog (Shh) is present in MPs generated from activated/apoptotic human T lymphocytes [Martínez et al., Blood (2006) vol. 108, 3012-3020]. We show here that Shh carried by MPs induces nitric oxide (NO) release from endothelial cells, triggers changes in the expression and phosphorylation of enzymes related to the NO pathway, and decreases production of reactive oxygen species. When PI3-kinase and ERK signaling were specifically inhibited, the effects of MPs were reversed. In vivo injection of MPs in mice was also able to improve endothelial function by increasing NO release, and it reversed endothelial dysfunction after ischemia/reperfusion. Silencing the effects of Shh with cyclopamine, a specific inhibitor of Shh, or siRNA, an inhibitor of the Shh receptor Patched, strongly reduced production of NO elicited by MPs. Taken together, we propose that the biological message carried by MPs harboring Shh may represent a new therapeutic approach against endothelial dysfunction during acute severe endothelial injury.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
Agouni, Abdelalia.agouni@surrey.ac.ukUNSPECIFIED
Mostefai, HAUNSPECIFIEDUNSPECIFIED
Porro, CUNSPECIFIEDUNSPECIFIED
Carusio, NUNSPECIFIEDUNSPECIFIED
Favre, JUNSPECIFIEDUNSPECIFIED
Richard, VUNSPECIFIEDUNSPECIFIED
Henrion, DUNSPECIFIEDUNSPECIFIED
Martínez, MCUNSPECIFIEDUNSPECIFIED
Andriantsitohaina, RUNSPECIFIEDUNSPECIFIED
Date : September 2007
Identification Number : 10.1096/fj.07-8079com
Copyright Disclaimer : Copyright 2007 Federation of American Society of Experimental Biology
Uncontrolled Keywords : Animals, Blotting, Western, Cells, Cultured, Electron Spin Resonance Spectroscopy, Endothelium, Vascular, Enzyme Inhibitors, Flow Cytometry, Hedgehog Proteins, Humans, Male, Mice, Microbodies, Nitric Oxide, Nitric Oxide Synthase Type III, Phosphatidylinositol 3-Kinases, Phosphorylation, Proto-Oncogene Proteins c-akt, RNA Interference, Reactive Oxygen Species, Signal Transduction, T-Lymphocytes, Trans-Activators, Transfection, Veratrum Alkaloids
Depositing User : Symplectic Elements
Date Deposited : 15 Aug 2017 14:58
Last Modified : 15 Aug 2017 14:58
URI: http://epubs.surrey.ac.uk/id/eprint/158182

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