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

Yang, Ying; Nie, Wei; Yuan, Jian‐Min; Zhang, Bingkun; Wang, Zhong; Wu, Zhenlong; Guo, Yuming

doi:10.3858/emm.2010.42.11.078

Cited by 26 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The studies of Tan had found that ET‐1 increased the expression of MMP‐2 and contributes to pulmonary vascular remodelling, and speculated increased vascular MMP‐2 might amplify its own expression through increased ET‐1 activity (Tan et al., ; ). Our results agree with previous reports on the phytoestrogen (Yang et al., ; Hassanpour et al., ). And, our findings indicate that Trifolium pratense isoflavone dietary treatment reduces ET‐1 levels in lungs and regulates the secretion of NO and ET‐1, thereby leading to a reduction of PAH.…”

Section: Discussionsupporting

confidence: 94%

Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens

Jiang

Yang

2015

Animal Physiology Nutrition

View full text Add to dashboard Cite

Pulmonary arterial remodelling is a pathological characteristic of pulmonary arterial hypertension (PAH), which contributes to the development of sustained pulmonary hypertension. The aim of this study was to investigate the effects of dietary Trifolium pratense isoflavones on pulmonary vascular remodelling in experimental broiler pulmonary hypertension syndrome. Exposure to sub-thermoneutral environmental temperatures increased broiler's pulmonary hypertension syndrome incidence and raised expression levels of nitric oxide, endothelin and endothelial nitric oxide synthase. Dietary supplementation (20 mg/kg basal diet) with Trifolium pratense isoflavones reduced pulmonary hypertension syndrome incidence and improved pulmonary vascular remodelling without affecting growth performance. The beneficial effect likely came from isoflavone improved pulmonary vascular remodelling. Isoflavone induced inducible nitric oxide synthase expression, which led to increased nitric oxide level. The nitric oxide could mediate vasorelaxation in the lungs. At the same time, the expression of endothelin was downregulated by isoflavone. Dietary supplementation of Trifolium pratense isoflavone might be a potential therapeutic strategy for the treatment of pulmonary hypertension.

show abstract

Section: Discussionsupporting

confidence: 94%

Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens

Jiang

Yang

2015

Animal Physiology Nutrition

View full text Add to dashboard Cite

show abstract

“…We found that Gen restored levels of cGMP and p-eNOS at Ser 1177 and p-Akt at Ser 473 in hypoxic lungs and pulmonary arteries. The protein kinase Akt has been proposed to phosphorylate eNOS at Ser 1177 and to increase eNOS activity in response to various stimuli in vascular endothelial cells (7), whereas Gen activated eNOS through a PI3K/Akt-dependent mechanism in pulmonary arterial endothelial cells (45). For the first time, however, the present study of HL rats demonstrated that Gen treatment upregulated the PI3K/Akt pathway in the lungs and pulmonary arteries.…”

Section: Discussionmentioning

confidence: 72%

Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system

Kuriyama

Morio

Toba

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system.

show abstract

“…Moreover, it has been shown to reverse in vitro the loss of T-cell signaling components at post-menopausal estrogen levels, with no significant effect at pre-menopausal estrogen levels [92]. In broiler pulmonary arterial endothelial cells genistein stimulated a rapid phosphorylation of eNOS activating the eNOS/NO axis; the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Aktdependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt [93].…”

Section: Effects Of Environmental Estrogens On the Immune Systemmentioning

confidence: 99%

The role of environmental estrogens and autoimmunity

Chighizola

Meroni

2012

Autoimmunity Reviews

View full text Add to dashboard Cite

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

Cited by 26 publications

References 37 publications

Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens

Trifolium pratense isoflavones improve pulmonary vascular remodelling in broiler chickens

Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system

The role of environmental estrogens and autoimmunity

Contact Info

Product

Resources

About