Zinc blocks gene expression of mitochondrial aconitase in human prostatic carcinoma cells.
Mitochondrial aconitase (mACON) contains a [4Fe-4S] cluster as the key enzyme for citrate oxidation in the human prostatic epithelial cell. Although there is accumulating evidence indicating that accumulation of high levels of zinc in prostate epithelial cells causes reduced efficiency of citrate oxidation, zinc regulation on the mACON is still not well understood. From in vitro studies, zinc chloride treatment has been developed using humic acid as the carrier (Zn-HA) in human prostatic carcinoma cells, PC-3. Zn-HA treatment (0.1-10 microM) restricts mACON enzymatic activity, which attenuates citrate utility and decreases intracellular ATP levels in PC-3 cells, whereas the effect is blocked by adding the zinc chelator, diethylenetriaminepentaacetic acid (DTPA). Immunoblot, ribonuclease-protection and transient gene-expression assays indicate that Zn-HA treatments inhibit mACON gene expression. Mutation of the putative metal response element (MRE) from CTCGCCTTCA to TGATCCTTCA abolishes Zn-HA inhibition of mACON promoter activity. Our results have demonstrated that zinc possesses a specific regulatory mechanism on the mACON gene, and a biologic function of the putative metal regulatory system in mACON gene transcription has been identified.
Tsui
Ke-Hung
KH
Department of Urology, Chang Gung Memorial Hospital, Kwei-Shan, Taiwan, Republic of China.
Chang
Phei-Lang
PL
Juang
Horng-Heng
HH
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D002951:Citrates / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics*; D020218:Response Elements; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds / Q000494:pharmacology*
D002712:Chlorides; D002951:Citrates; D017967:Zinc Compounds; C016837:zinc chloride; D000255:Adenosine Triphosphate; D000154:Aconitate Hydratase