Prudova Anna, Albin Matthias, Bauman Zachary, Lin Alexander, Vitvitsky Victor, Banerjee Ruma
Redox Biology Center and the Biochemistry Department, University of Nebraska, Lincoln, Nebraska, USA.
Antioxid Redox Signal. 2007 Nov;9(11):1875-81. doi: 10.1089/ars.2007.1712.
Clearance of homocysteine via the transsulfuration pathway provides an endogenous route for cysteine synthesis and represents a quantitatively significant source of this amino acid needed for glutathione synthesis. Men have higher plasma levels of total homocysteine than do women, but the mechanism of this sex-dependent difference is not known. In this study, we investigated regulation by testosterone of cystathionine beta-synthase (CBS), which catalyzes the committing step in the transsulfuration pathway. We report that testosterone downregulates CBS expression via a posttranscriptional mechanism in the androgen-responsive prostate cancer cell line, LNCaP. This diminution in CBS levels is accompanied by a decrease in flux through the transsulfuration pathway and by a lower intracellular glutathione concentration. The lower antioxidant capacity in testosterone-treated prostate cancer cells increases their susceptibility to oxidative stress conditions. These results demonstrate regulation of the homocysteine-clearing enzyme, CBS, by testosterone and suggest the potential utility of targeting this enzyme as a chemotherapeutic strategy.
通过转硫途径清除同型半胱氨酸为半胱氨酸合成提供了一条内源性途径，并且是谷胱甘肽合成所需的这种氨基酸的一个数量上显著的来源。男性血浆总同型半胱氨酸水平高于女性，但这种性别依赖性差异的机制尚不清楚。在本研究中，我们研究了睾酮对胱硫醚β-合酶（CBS）的调节作用，该酶催化转硫途径中的关键步骤。我们报告，在雄激素反应性前列腺癌细胞系LNCaP中，睾酮通过转录后机制下调CBS表达。CBS水平的这种降低伴随着转硫途径通量的减少以及细胞内谷胱甘肽浓度的降低。睾酮处理的前列腺癌细胞中较低的抗氧化能力增加了它们对氧化应激条件的敏感性。这些结果证明了睾酮对同型半胱氨酸清除酶CBS的调节作用，并提示将该酶作为一种化疗策略的潜在效用。
