Article

Genistein activates endothelial nitric oxide synthase in broiler pulmonary arterial endothelial cells by an Akt-dependent mechanism.

State key Lab of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
Experimental and Molecular Medicine (Impact Factor: 2.46). 10/2010; 42(11):768-76. DOI: 10.3858/emm.2010.42.11.078
Source: PubMed

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.

0 Bookmarks
 · 
81 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Andrographolide (AND) and neoandrographolide (NEO) are the diterpenoids from the Andrographis paniculata (Acanthaceae). It is reported the diterpenoids exhibit a wide spectrum of biological activities. The aim of this study was to investigate the hypolipidemic effect of AND and NEO in hyperlipidemic mice induced by 75% yolk emulsion and in hyperlipidemic rats induced by high fat emulsion, respectively. The results showed that the levels of triglyceride, total cholesterol (TC) and low-density lipoprotein cholesterol were reduced by AND and NEO in a dose-dependent tendency in mice. Compared with the model group, the plasma TC levels of experimental groups with AND and NEO at 100 mg/kg dosage decreased by 23.9 and 20.2% in rats, respectively (P < 0.05). It was also found that the plasma aspartate transaminase and alanine transaminase levels were significantly decreased by feeding with AND and NEO in rats, compared with positive group (simvastatin) (P < 0.01). Otherwise, AND and NEO could protect the cardiovascular due to down-regulation of iNOS expression and up-regulation of eNOS expression. In conclusion, AND and NEO have potent hypolipidemic effects and protect the cardiovascular without significant liver damage. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 06/2012; · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Flavonoids, a family of polyphenols, generally found in various fruits and vegetables, as well as in many plant beverages such as tea, pomegranate juice, raspberry, blueberries, and red wine. Recently, studies on flavonoids have attracted scientific attention as a potential nutritional strategy to prevent a broad range of chronic disorders. Many studies suggest that consumption of these flavonoids in sufficient amount plays neuroprotective, cardioprotective, anti-inflammatory, and chemopreventive roles. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids and their in vivo metabolites do not act only as conventional antioxidants but may also exert modulatory actions on cellular system through direct action on various signalling pathways. These pathways include phosphoinositide 3-kinase, Akt/protein kinase B, mitogen-activated protein kinase, tyrosine kinases, and protein kinase C. Various inhibitory or stimulatory actions of flavonoids on these pathways greatly affect cellular functions by altering the phosphorylation state of targeted molecules. In addition, flavonoids also modulate various gene expressions through activation of various transcription factors. Thus, the present review will bestow a breathing overview regarding the prime role of flavonoids in modulation of survival signalling pathways at cellular system.
    Genes & Nutrition 05/2014; 9(3):400. · 3.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Porphyromonas gingivalis infection and cathepsins protease upregulation are independently implicated in atherosclerosis worsening. In this study, we evaluated the effects of P. gingivalis infection and P. gingivalis -purified lipopolysaccharide (Pg-LPS) stimulation on the expression of cathepsin B (CATB) in endothelial cells (ECs). Analysis of the enzymatic activity and expression of CATB were investigated at the messenger RNA, protein and protein-phosphorylation levels. Effects of Toll-like receptors 2 and 4 blocking on CATB activity were also analysed. Our results showed that P. gingivalis and Pg-LPS significantly increased the activity of CATB but with different kinetics. The peak of CATB activity was observed 3 h after P. gingivalis infection but it appeared 48 h after Pg-LPS stimulation. The increase of CATB activity was related to its rapid tyrosine-dephosphorylation during P. gingivalis infection, whereas the levels of CATB messenger RNAs and proteins did not vary after P. gingivalis infection or Pg-LPS stimulation. Inhibition of Toll-like-receptors 2 and 4 differentially decreased P. gingivalis and Pg-LPS CATB activations. These results showed for the first time that P. gingivalis infection rapidly affects ECs and modulates CATB activity, whereas Pg-LPS effects appear to be delayed. This study suggests that direct infection of ECs by P. gingivalis may worsen atherosclerotic plaque formation via activation of the CATB pathway.
    Molecular oral microbiology. 06/2012; 27(3):137-48.

Preview

Download
0 Downloads
Available from