| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 28, 2004
Accepted on August 10, 2004
From: Division of Endocrinology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa and Veterans Administration Medical Center, Iowa City, Iowa 52246, USA
* To whom correspondence should be addressed. E-mail: joseph-dillon{at}uiowa.edu.
Genistein may improve vascular function but the mechanism of this effect is unclear. We tested the hypothesis that genistein directly regulates vascular function through stimulation of endothelial nitric oxide synthesis. Genistein activated endothelial nitric oxide synthase (eNOS) in intact bovine aortic endothelial cells and human umbilical vein endothelial cells, over an incubation period of 10 min. The maximal eNOS activity was at 1 µM genistein. Consistent with this activation pattern, 1 µM genistein maximally stimulated the phosphorylation of eNOS at serine 1179, at 10 min of incubation. The rapid activation of eNOS by genistein was not dependent on RNA transcription or new protein synthesis, and was not blocked by a specific estrogen receptor antagonist. In addition, inhibition of mitogen-activated protein kinase or phosphatidylinositol 3-OH kinase/Akt kinase had no affect on eNOS activation by genistein. Furthermore, the genistein effect on eNOS was also independent of tyrosine kinase inhibition. However, inhibition of cAMP-dependent kinase (PKA) by H89 completely abolished the genistein-stimulated eNOS activation and phosphorylation, suggesting that genistein acted through a PKA-dependent pathway. These findings demonstrated that genistein had direct non-genomic effects on eNOS activity in vascular endothelial cells, leading to eNOS activation and NO synthesis. These effects were mediated by PKA and were unrelated to an estrogenic effect. This cellular mechanism may underlie some of the cardiovascular protective effects proposed for soy phytoestrogens.
This article has been cited by other articles:
 |
|
 |
|
  D. Liu, M. Iruthayanathan, L. L. Homan, Y. Wang, L. Yang, Y. Wang, and J. S. Dillon Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms Endocrinology, March 1, 2008; 149(3): 889 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Si and D. Liu Genistein, a Soy Phytoestrogen, Upregulates the Expression of Human Endothelial Nitric Oxide Synthase and Lowers Blood Pressure in Spontaneously Hypertensive Rats J. Nutr., February 1, 2008; 138(2): 297 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mann, D. J. Rowlands, F. Y.L. Li, P. de Winter, and R. C.M. Siow Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression Cardiovasc Res, July 15, 2007; 75(2): 261 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Liu, H. Si, K. A. Reynolds, W. Zhen, Z. Jia, and J. S. Dillon Dehydroepiandrosterone Protects Vascular Endothelial Cells against Apoptosis through a G{alpha}i Protein-Dependent Activation of Phosphatidylinositol 3-Kinase/Akt and Regulation of Antiapoptotic Bcl-2 Expression Endocrinology, July 1, 2007; 148(7): 3068 - 3076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Erdman Jr., D. Balentine, L. Arab, G. Beecher, J. T. Dwyer, J. Folts, J. Harnly, P. Hollman, C. L. Keen, G. Mazza, et al. Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC J. Nutr., March 1, 2007; 137(3): 718S - 737S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Xiao, J. Mei, W. Huang, C. Wood, M. R. L'Abbe, G. S. Gilani, G. M. Cooke, and I. H. Curran Dietary Soy Protein Isolate Modifies Hepatic Retinoic Acid Receptor-{beta} Proteins and Inhibits Their DNA Binding Activity in Rats J. Nutr., January 1, 2007; 137(1): 1 - 6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Joy, R. C. M. Siow, D. J. Rowlands, M. Becker, A. W. Wyatt, P. I. Aaronson, C. W. Coen, I. Kallo, R. Jacob, and G. E. Mann The Isoflavone Equol Mediates Rapid Vascular Relaxation: Ca2+-INDEPENDENT ACTIVATION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE/Hsp90 INVOLVING ERK1/2 AND Akt PHOSPHORYLATION IN HUMAN ENDOTHELIAL CELL J. Biol. Chem., September 15, 2006; 281(37): 27335 - 27345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Peluso Flavonoids Attenuate Cardiovascular Disease, Inhibit Phosphodiesterase, and Modulate Lipid Homeostasis in Adipose Tissue and Liver Experimental Biology and Medicine, September 1, 2006; 231(8): 1287 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Cruz, L. Luksha, H. Logman, L. Poston, S. Agewall, and K. Kublickiene Acute responses to phytoestrogens in small arteries from men with coronary heart disease Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1969 - H1975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, W. Zhen, Z. Yang, J. D. Carter, H. Si, and K. A. Reynolds Genistein Acutely Stimulates Insulin Secretion in Pancreatic {beta}-Cells Through a cAMP-Dependent Protein Kinase Pathway. Diabetes, April 1, 2006; 55(4): 1043 - 1050. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
