RRC ID 121
Author Xu JW, Ikeda K, Yamori Y.
Title Genistein inhibits expressions of NADPH oxidase p22phox and angiotensin II type 1 receptor in aortic endothelial cells from stroke-prone spontaneously hypertensive rats.
Journal Hypertens Res
Abstract Phytoestrogens are considered to be natural selective estrogen receptor modulators exerting antioxidant activity and improving vascular function. However, the mechanisms responsible for their antioxidative effects remain largely unknown. This study tested the hypothesis that genistein may provide significant endothelial protection by antioxidative effects through attenuating NADPH oxidase expression and activity. The results showed that genistein suppressed the expressions of the p22phox NADPH oxidase subunit and angiotensin II (Ang II) type 1 (AT1) receptor in a concentration- and time-dependent manner in aortic endothelial cells from stroke-prone spontaneously hypertensive rats examined by Western blot analysis. Treatment with genistein also remarkably reduced the Ang II-induced superoxide by the reduction of nitroblue tetrazolium, inhibited nitrotyrosine formation, and attenuated endothelin-1 production by ELISA via the stimulation of Ang II. However, when cells were pretreated with ICI-182780, an estrogen-receptor antagonist, at a concentration of 50 micromol/l for 30 min and then co-incubated with ICI-182780 and genistein for 24 h, the inhibitory effect of genistein was not blocked. In contrast, the inhibitory effect of genistein treatment was partially reversed by 30-min pretreatment of endothelial cells with GW9662, a peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist. Genistein thus appears to act as an antioxidant at the transcription level by the downregulation of p22phox and AT1 receptor expression. Our data also showed that the PPARgamma pathway was involved, at least in part, in the inhibitory effect of genistein on the expression of p22phox and AT1 receptors. The endothelial-protective effects of phytoestrogen may contribute to improvement of cardiovascular functions.
Volume 27(9)
Pages 675-83
Published 2004-9-1
DOI 10.1291/hypres.27.675
PII JST.JSTAGE/hypres/27.675
PMID 15750262
MeSH Angiotensin II / pharmacology Anilides / pharmacology Animals Aorta, Thoracic / cytology Cells, Cultured Endothelin-1 / metabolism Endothelium, Vascular / cytology Endothelium, Vascular / drug effects* Endothelium, Vascular / enzymology Enzyme Inhibitors / pharmacology* Estradiol / analogs & derivatives* Estradiol / pharmacology Estrogen Antagonists / pharmacology Fulvestrant Genistein / pharmacology* Hypertension / metabolism* Male Membrane Transport Proteins / metabolism* NADPH Dehydrogenase / metabolism* NADPH Oxidases PPAR gamma / antagonists & inhibitors Phosphoproteins / metabolism* Rats Rats, Inbred SHR Receptor, Angiotensin, Type 1 / metabolism* Signal Transduction / drug effects Signal Transduction / physiology Stroke / metabolism Superoxides / metabolism Tyrosine / analogs & derivatives* Tyrosine / metabolism Vasoconstrictor Agents / pharmacology
IF 2.941
Times Cited 37
Rats SHRSP/Izm(strainID=409)