期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 9, 期 11, 页码 1875-1881出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2007.1712
关键词
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资金
- NIDDK NIH HHS [DK64959] Funding Source: Medline
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.
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