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Nitroprusside stimulates mitochondrial aconitase gene expression through the cyclic adenosine 3′,5′‐monosphosphate signal transduction pathway in human prostate carcinoma cells
Author(s) -
Juang HorngHeng
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20084
Subject(s) - sodium nitroprusside , aconitase , gene expression , signal transduction , enzyme , nitric oxide , biology , gene , microbiology and biotechnology , chemistry , biochemistry , endocrinology
BACKGROUGD Mitochondrial aconitase (mACON), an iron‐requiring enzyme, is a major target of nitric oxide (NO) in cells, which causes the oxidant‐mediated disruption of the [4Fe‐4S] prosthetic group of the enzyme. In this study, the effect of NO on m ACON enzymatic activity and gene expression were investigated. MEHTODS Three NO generators, sodium nitroprusside (SNP), S ‐nitoso‐ N ‐acetylpenicillamine (SNAP), and 3‐morpholinosydnonimine (SIN) were used to determine the regulation of mACON enzymatic activity by NO. The effect of SNP on mACON, which modulates citrate secretion and cellular bioenergetics in PC‐3 cells, was investigated by determining the effect of SNP on m ACON gene expression using Western blot and transient gene expression assays. RESULTS SNP upregulated m ACON enzymatic activity and gene expression in PC‐3 cells. However, treating cells with other NO generators, SNAP and SIN, resulted in decreased mACON enzymatic activity. The addition of ascorbic acid to the SNP treatment resulted in a decrease in m ACON enzymatic activity and gene expression. Our results showed that both SNP and dibutyryl‐cAMP increased the mACON promoter activity 2‐fold while the effect was blocked by adding H‐89. Mutation of the cAMP response element (CRE) to the AGAGCT abolished the activating effects of SNP and dibutyryl‐cAMP on mACON promoter activity. CONCLUSIONS These results establish the function of nitroprusside as a signaling molecule for m ACON gene expression through the cAMP signal transduction pathway in human prostatic carcinoma cells. © 2004 Wiley‐Liss, Inc.