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Titre du document / Document title

Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells

Auteur(s) / Author(s)

YANG SUN (1) ; SUMI Daigo (1) ; KUMAGAI Yoshito (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Sciences, University of Tsukuha, JAPON

Résumé / Abstract

Although 2,4,6-trinitrotoluene (TNT) has been found to uncouple nitric oxide synthase (NOS), thereby leading to reactive oxygen species (ROS), cellular response against TNT still remains unclear. Exposure of bovine aortic endothelial cells (BAECs) to TNT (100 μM) resulted in serine 1179 phosphorylation of endothelial NOS (eNOS). With specific inhibitors (wortmannin and LY294002), we found that PI3K/Akt signaling participated in the eNOS phosphorylation caused by TNT, whereas the ERK pathway did not. ROS were generated following exposure of BAECs to TNT. However, TNT-mediated phosphorylation of either eNOS or Akt was drastically blocked by NAC and PEG-CAT. Interestingly, pretreatment with apocynin, a specific inhibitor for NADPH oxidase, diminished the phosphorylation of eNOS and Akt. These results suggest that TNT affects NADPH oxidase, thereby generating hydrogen peroxide, which is capable of activating PI3K/Akt signaling associated with eNOS Ser 1179 phosphorylation.

Revue / Journal Title

Toxicology and applied pharmacology    ISSN  0041-008X   CODEN TXAPA9 

Source / Source

2006, vol. 214, no1, pp. 55-60 [6 page(s) (article)] (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1959) (Revue)

Mots-clés anglais / English Keywords

Aminoacid

;

Transferases

;

Enzyme

;

Oxidoreductases

;

Hydrogenperoxides

;

Signal transduction

;

Akt protein kinase

;

1-Phosphatidylinositol 3-kinase

;

Trinitrotoluene

;

Nitric-oxide synthase

;

Hydrogen peroxide

;

Endothelial cell

;

Phosphorylation

;

Serine

;

Mots-clés français / French Keywords

Aminoacide

;

Transferases

;

Enzyme

;

Oxidoreductases

;

Hydrogénoperoxyde

;

Transduction signal

;

Akt protein kinase

;

1-Phosphatidylinositol 3-kinase

;

Toluène(trinitro)

;

Nitric-oxide synthase

;

Hydrogène peroxyde

;

Cellule endothéliale

;

Phosphorylation

;

Sérine

;

Mots-clés espagnols / Spanish Keywords

Aminoácido

;

Transferases

;

Enzima

;

Oxidoreductases

;

Hidrogenoperóxido

;

Transducción señal

;

Akt protein kinase

;

1-Phosphatidylinositol 3-kinase

;

Tolueno(trinitro)

;

Nitric-oxide synthase

;

Peróxido de hydrogeno

;

Célula endotelial

;

Fosforilación

;

Serina

;

Mots-clés d'auteur / Author Keywords

TNT

;

PI3K

;

Akt

;

eNOS

;

Phosphorylation

;

Hydrogen peroxide

;

Endothelial cell

;

Localisation / Location

INIST-CNRS, Cote INIST : 9067, 35400013892857.0080

Nº notice refdoc (ud4) : 17900204



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