Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury

Shang Zhong Xu, Wenwen Zhong, Maryam Ghavideldarestani, Rahul Saurabh, Steve W. Lindow, Stephen Atkin

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Diabetic vascular complications are related to a combination of oxidative stress and hyperglycemia. Here we investigate the effect and mechanism of soy isoflavones on oxidative stress-induced endothelial cell injury. Oxidative stress was modeled in primary cultured human umbilical vein endothelial cells by incubation with H2O2 and high glucose. Genistein and daidzein protected the cells against H2O2-induced apoptosis and their protective actions were abolished by ICI 182780, an estrogen receptor antagonist. The inhibition of cell proliferation by oxidative stress was prevented by genistein and daidzein under normal glucose conditions, but they were less effective at high glucose levels. Genistein and daidzein upregulated the estrogen receptor ERβ and increased Bcl-2 expression. Silencing of Bcl-2 with siRNA abolished the protection of genistein. Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by wortmannin and Y-27632 altered the effects of genistein and daidzein on cell survival. We conclude that oxidative stress-induced apoptosis and cell proliferation inhibition can be prevented by soy isoflavones via the regulation of ERβ and Bcl-2/Bax expression and modulation of cell survival signaling, such as the PI3K pathway. These findings imply that multiple mechanisms are involved in the beneficial effects of soy isoflavone supplements for diabetic endothelial injury.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalFree Radical Biology and Medicine
Volume47
Issue number2
DOIs
Publication statusPublished - 15 Jul 2009
Externally publishedYes

Fingerprint

Isoflavones
Oxidative stress
Genistein
Endothelium
Oxidative Stress
Wounds and Injuries
Endothelial cells
Cell proliferation
Phosphatidylinositol 3-Kinases
Glucose
Cell Survival
Cell Proliferation
Apoptosis
Cell signaling
Diabetic Angiopathies
rho-Associated Kinases
Human Umbilical Vein Endothelial Cells
Hyperglycemia
Estrogen Receptors
Small Interfering RNA

Keywords

  • Endothelial cells
  • Free radicals
  • Hyperglycemia
  • Oxidative stress
  • Phytoestrogens

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury. / Xu, Shang Zhong; Zhong, Wenwen; Ghavideldarestani, Maryam; Saurabh, Rahul; Lindow, Steve W.; Atkin, Stephen.

In: Free Radical Biology and Medicine, Vol. 47, No. 2, 15.07.2009, p. 167-175.

Research output: Contribution to journalArticle

Xu, Shang Zhong ; Zhong, Wenwen ; Ghavideldarestani, Maryam ; Saurabh, Rahul ; Lindow, Steve W. ; Atkin, Stephen. / Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 2. pp. 167-175.
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