Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism.
10.3858/emm.2010.42.11.078
- Author:
Ying YANG
1
;
Wei NIE
;
Jianmin YUAN
;
Bingkun ZHANG
;
Zhong WANG
;
Zhenlong WU
;
Yuming GUO
Author Information
1. State key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University (CAU), Beijing 100193, China. bio2046@hotmail.com
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
endothelial cells;
genistein;
nitric oxide synthase type III;
proto-oncogene proteins c-akt;
pulmonary artery
- MeSH:
Animals;
Cell Line;
Chickens;
Disease Models, Animal;
Endothelium, Vascular/drug effects/*metabolism/pathology;
Enzyme Activation/drug effects;
Female;
Genistein/*pharmacology;
Humans;
Hypertension, Pulmonary/drug therapy/*metabolism/pathology;
Nitric Oxide Synthase Type III/genetics/*metabolism;
Oncogene Protein v-akt/*metabolism;
Phosphorylation;
Signal Transduction/drug effects
- From:Experimental & Molecular Medicine
2010;42(11):768-776
- CountryRepublic of Korea
- Language:English
-
Abstract:
Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser(1179) which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models.
