Phytoestrogen Genistein Protects Against Endothelial Barrier Dysfunction in Vascular Endothelial Cells Through PKA-Mediated Suppression of RhoA Signaling
作者： Zhenquan Jia , Wei Zhen , Pon Velayutham Anandh Babu , Dongmin Liu
DOI: 10.1210/EN.2012-1774
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摘要: The soy-derived phytoestrogen genistein has received attention for its potential to improve vascular function, but mechanism remains unclear. Here, we report that at physiologically relevant concentrations (0.1–10 μM) significantly inhibited thrombin-induced increase in endothelial monolayer permeability. Genistein also reduced the formation of stress fibers by thrombin and suppressed phosphorylation myosin light chain (MLC) on Ser19/Thr18 cells (ECs). had no effect resting intracellular [Ca2+] or Ca2+ mobilization. Addition inhibitors nitric oxide synthase estrogen receptor did not alter protective genistein. RhoA is a small GTPase plays an important role actin-myosin contraction barrier dysfunction. inhibitor blocked permeability ablated MLC-phosphorylation ECs. Inhibit...
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endojournals.org参考文章(68)
Y. T. van der Schouw, P. H. M. Peeters, D. E. Grobbee, M. J. J. de Kleijn, Phyto-oestrogens and cardiovascular disease risk. Nutrition Metabolism and Cardiovascular Diseases. ,vol. 10, pp. 154- 167 ,(2000)
Victor W.M. van Hinsbergh, Rudi G.J. Westendorp, Richard Draijer, Edo Meinders, Cyclic-GMP-mediated decrease in permeability of human umbilical and pulmonary artery endothelial cell monolayers. Journal of Vascular Research. ,vol. 31, pp. 42- 51 ,(1994) , 10.1159/000159030
T. Akiyama, J. Ishida, S. Nakagawa, H. Ogawara, S. Watanabe, N. Itoh, M. Shibuya, Y. Fukami, Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry. ,vol. 262, pp. 5592- 5595 ,(1987) , 10.1016/S0021-9258(18)45614-1
Xia Xu, Keecha S. Harris, Huei-Ju Wang, Patricia A. Murphy, Suzanne Hendrich, Bioavailability of Soybean Isoflavones Depends upon Gut Microflora in Women The Journal of Nutrition. ,vol. 125, pp. 2307- 2315 ,(1995) , 10.1093/JN/125.9.2307
Carolyn E. Patterson, Hazel Lum, Kane L. Schaphorst, Alexander D. Verin, Joeg N. Garcia, Regulation of Endothelial Barrier Function by the cAMP-Dependent Protein Kinase Endothelium-journal of Endothelial Cell Research. ,vol. 7, pp. 287- 308 ,(2000) , 10.3109/10623320009072215
R. Morandini, G. Ghanem, A. Portier-Lemarie, B. Robaye, A. Renaud, J. M. Boeynaems, Action of cAMP on expression and release of adhesion molecules in human endothelial cells American Journal of Physiology. ,vol. 270, ,(1996) , 10.1152/AJPHEART.1996.270.3.H807
H Kim, T G Peterson, S Barnes, Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways The American Journal of Clinical Nutrition. ,vol. 68, ,(1998) , 10.1093/AJCN/68.6.1418S
Lothar Schweigerer, Theodore Fotsis, Herman Adlercreutz, Michael Pepper, Roberto Montesano, Tapio Hase, Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis. Journal of Nutrition. ,vol. 125, ,(1995) , 10.1093/JN/125.SUPPL_3.790S
R A King, D B Bursill, Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. The American Journal of Clinical Nutrition. ,vol. 67, pp. 867- 872 ,(1998) , 10.1093/AJCN/67.5.867
Kerry E Wangen, Alison M Duncan, Xia Xu, Mindy S Kurzer, Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women The American Journal of Clinical Nutrition. ,vol. 73, pp. 225- 231 ,(2001) , 10.1093/AJCN/73.2.225