Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells

Ke Hung Tsui, Phei Lang Chang, Horng Heng Juang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

Aim: To investigate the possible role of manganese in the regulation of mitochondrial aconitase (mACON) activity human prostate carcinoma cell line PC-3 cells. Methods: The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electro-phoretic mobility-shift assays. Results: In vitro study revealed that manganese chloride (MnCl2) treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC-3 cells. Although results from transient gene expression assays showed that MnCl2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by co-treatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCl2 on the gene expression of mACON. Conclusion: These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.

Original languageEnglish
Pages (from-to)307-315
Number of pages9
JournalAsian Journal of Andrology
Volume8
Issue number3
DOIs
StatePublished - 05 2006

Keywords

  • Adenosine triphosphate
  • Citrate
  • Metal response element
  • PC-3
  • Proliferation
  • Prostate carcinoma cell line

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