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

作     者：Ke-Hung Tsui Phei-Lang Chang Horng-Heng Juang 

作者机构：Department of UrologyChang Gung Molecular Image CenterChang Gung Memorial Hospital Department of UrologyChang Gung Memorial Hospital Chang Gung Molecular Image CenterChang Gung Memorial Hospital Department of AnatomyChang Gung UniversityKwei-Shan.Tao-Yuan 333TaiwanChina 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2006年第8卷第3期

页      面：307-315,387页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This study was supported by research grants CMRP G1006 and G34026 from Chang Gung Memorial Hospital and by grants NSC 94-2320-B-182-017 and NSC 94-2314-B-182A-155 from the National Science Council 

主　　题：citrate adenosine triphosphate proliferation PC-3 metal response element prostate carcinoma cell line 

摘      要：Aim:To investigate the possible role of manganese in the regulation of mitochondrial aconitase(mACON)activity human prostate carcinoma cell line PC-3 ***:The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dmucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the *** putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electro- phoretic mobility-shift ***:In vitro study revealed that manganese chloride(MnCl2)treatment for 16h inhibited the enzymatic activity of mACON,which induced the inhibition of citrate utility and cell proliferation of PC- 3 *** results from transient gene expression assays showed that MnCl_2,treatment upregulated gene translation by approximately 5-fold through the iron response element pathway,immunoblot and reporter assays showed that MnCl_2 treatments inhibited protein and gene expression of *** effect was reversed by co- treatment with fenic ammonium *** 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 MnCl_2 on the gene expression of ***: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.