Inhibition of XO or NOX attenuates diethylstilbestrol-induced endothelial nitric oxide deficiency without affecting its effects on LNCaP cell invasion and apoptosis.

Clinical Science
Ji-Youn YounHua Cai

Abstract

Oestrogen protects cardiovascular health partially via an up-regulation of NO• (NO radical) production. Its synthetic analogue DES (diethylstilbestrol), used as a potent androgen deprivation therapy for patients with prostate cancer, is however associated with high incidence of thromboembolic events. Exposure of BAECs (bovine aortic endothelial cells) to pharmacologically relevant dosage (12.5 μmol/l, 24 h) of DES resulted in a marked reduction in endothelial NO• bioavailability determined by ESR (electron spin resonance), while 17β-oestradiol instead increased NO• production as expected. Intriguingly, endothelial O(2)•- (superoxide anion) production was up-regulated by DES in vitro and in vivo, which was, however, attenuated by the ER (oestrogen receptor) antagonist ICI 182780, the XO (xanthine oxidase) inhibitor oxypurinol or the NOX (NADPH oxidase) inhibitor NSC23766. These agents also restored NO• production. DES alone in a cell-free system did not produce any ESR-sound O(2)•- signal. Of note, eNOS (endothelial NO synthase) mRNA and protein remained unchanged in response to DES. These results suggest that receptor-dependent activation of XO or NOX, and subsequent production of O(2)•-, mediate DES-induced NO• deficiency. Thi...Continue Reading

References

Jul 3, 1996·Journal of the National Cancer Institute·C N RobertsonR L Fine
Jun 11, 1999·The New England Journal of Medicine·M E Mendelsohn, R H Karas
Nov 14, 2000·Circulation Research·H Cai, D G Harrison
Oct 20, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A H WagnerM Hecker
Jun 25, 2002·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Avedis Meneshian, Gregory B Bulkley
Jul 13, 2002·Annals of the New York Academy of Sciences·Maria C CidHynda K Kleinman
Aug 29, 2002·Seminars in Urologic Oncology·Frans Debruyne
Dec 21, 2002·The Journal of Biological Chemistry·Ulrich LaufsGeorg Nickenig
Mar 27, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Julie LassurguèreBernard Jégou
Jun 17, 2004·American Heart Journal·Kimon S StamatelopoulosStamatios F Stamatelopoulos
Apr 27, 2005·Seminars in Reproductive Medicine·Janice D Wagner, Thomas B Clarkson
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Karel Chalupsky, Hua Cai
Jun 14, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Jean-Jacques KalachJean André
Jun 21, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Muthuvel JayachandranVirginia M Miller
Jun 7, 2006·JAMA : the Journal of the American Medical Association·Victor G VogelUNKNOWN National Surgical Adjuvant Breast and Bowel Project (NSABP)
May 26, 2007·Stroke; a Journal of Cerebral Circulation·Alyson A MillerChristopher G Sobey
Jun 14, 2008·Journal of the American College of Cardiology·Joshua M HareUNKNOWN OPT-CHF Investigators
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alfonso Quintás-Cardama, Jorge Cortes

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