Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells.

Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Research Abstract Details 

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Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Abstract Text:

A B El-Remessy,M Al-Shabrawey,D H Platt,M Bartoli,M A Behzadian,N Ghaly,N Tsai,K Motamed,R B Caldwell,

The modulation of angiogenic signaling by reactive oxygen species (ROS) is an emerging area of interest in cellular and vascular biology research. We provide evidence here that peroxynitrite, the powerful oxidizing and nitrating free radical, is critically involved in transduction of the VEGF signal. We tested the hypothesis that VEGF induces peroxynitrite formation, which causes tyrosine phosphorylation and mediates endothelial cell migration and tube formation, by studies of vascular endothelial cells in vitro and in a model of hypoxia-induced neovascularization in vivo. The specific peroxynitrite decomposition catalyst FeTPPs blocked VEGF-induced phosphorylation of VEGFR2 and c-Src and inhibited endothelial cell migration and tube formation. Furthermore, exogenous peroxynitrite mimicked VEGF activity in causing phosphorylation of VEGFR2 and stimulating endothelial cell growth and tube formation in vitro and new blood vessel growth in vivo. The selective nitration inhibitor epicatechin enhanced VEGF's angiogenic function in activating VEGFR2, c-Src, and promoting endothelial cell growth, migration, and tube formation in vitro and retinal neovascularization in vivo. Decomposing peroxynitrite with FeTPPs or blocking oxidation using the thiol donor NAC blocked VEGF's angiogenic functions in vitro and in vivo. In conclusion, peroxynitrite is critically involved in transducing VEGF's angiogenic signal via nitration-independent and oxidation-mediated tyrosine phosphorylation.

Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Publishing Authors By Initials

AB El-Remessy,M Al-Shabrawey,DH Platt,M Bartoli,MA Behzadian,N Ghaly,N Tsai,K Motamed,RB Caldwell,

For similar peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research abstracts see: peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research

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Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 2528-39

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 23

MONTH: 03

YEAR: 2007

Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor A

MESH TERMS: physiology

Chemical & Substance for Abstract: Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells. Information

Substance Name: Peroxynitrous Acid

Registry Number: 14691-52-2

Grant and Affiliation Information for Peroxynitrite mediates VEGF's angiogenic signal and function via a nitration-independent mechanism in endothelial cells.

AFFILIATION: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Athens, USA. aelremessy@mcg.edu

Country: United States

AGENCY: United States NEI

GRANT: EY11766

ACRONYM: EY

MEDLINETA: FASEB J

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