Homocysteine and copper interact to promote type 5 phosphodiesterase expression in rabbit cavernosal smooth muscle cells
Homocysteine and copper interact to promote type 5 phosphodiesterase expression in rabbit cavernosal smooth muscle cells作者机构：Department of Urology University of BristoL Bristol BS8 1TH UK Department of Cardiac Surgery University of BristoL Bristol BS8 1TH UK
出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)
年 卷 期：2008年第10卷第6期
页 面：905-913页
核心收录：
学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
基 金：WethanktheRalphShackmanTrustforfinancialsupport
主 题：erectile dysfunction superoxide PDE5 sildenafil
摘 要：Aim： To study the effects of homocysteine and copper on type 5 phosphodiesterase （PDE5） expression in cavemosai vascular smooth muscle cells （CVSMCs） and to investigate superoxide （O2-） derived from nicotinamide adenine dinucleotide phosphate oxidase as homocysteine and copper generate O2-, and O2- upregulates PDE5 expression. Methods： CVSMCs derived from rabbit penis were incubated with homocysteine or copper chloride with or without superoxide dismutase （SOD）, catalase, sildenafil citrate, or apocynin （nicotinamide adenine dinucleotide phosphate inhibitor） for 16 h. The expression of PDE5 and of glyceraldehyde-3-phosphate dehydrogenase （internal standard） was assessed using Western blot analysis. In parallel, O2-was measured spectrophotometrically. Results： CuCl2 alone （up to 10 μmol/L） and homocysteine alone （up to 100 μmol/L） had no effect on O2- formation in CVSMCs compared to controls. In combination, however, homocysteine and CuCl2 markedly increased O2- formation, an effect blocked by SOD, catalase, apocynin, and sildenafil （1 μmol/L） when co-incubated over the same time course. PDE5 expression was also significantly increased in CVSMCs incubated with homocysteine and CuCl2, compared to controls. This effect was also negated by 16-h co-incubation with SOD, catalase, apocynin and sildenafil. Conclusion： This represents a novel pathogenic mechanism underlying ED, and indicates that the therapeutic actions of prolonged sildenafil use are mediated in part through inhibition of this pathway.
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