Cholesterol modulation of the expression of mitochondrial aconitase in human prostatic carcinoma cells.
Mitochondrial aconitase (mACON) is the key enzyme for the citrate oxidation in the mitochondrial Krebs cycle. Cholesterol treatment (10 microg/ml of cholesterol and 1 microg/ml of 25-hydroxycholesterol) for 24 h stimulates mACON enzymatic activity in human prostatic carcinoma cells (PC-3) and hepatoma cells (HepG2). Mevastatin, a cholesterol synthesis antagonist, blocked the effect of cholesterol treatment on mACON. The cholesterol treatment stimulated mACON enzymatic activity, which enhanced the citrate utility but decreased intracellular ATP levels in PC-3 cells. The immunoblotting and transient gene expression assays demonstrated that cholesterol treatment enhances the gene expression of mACON. Mutation of the putative sterol response element (SRE) from GACGCCCCACT to GACGCCCATAT abolished the stimulating effects of cholesterol on the promoter activity of mACON gene. The results suggest that cholesterol treatment induces the mACON gene expression through the SRE signal transduction pathway. Our study demonstrated the deregulation of cholesterol on the citrate metabolism.
Feng
Tsui-Hsia
TH
Department of Nursing, Chang Gung University Tao-Yuan, Taiwan, ROC.
Tsui
Ke-Hung
KH
Juang
Horng-Heng
HH
D000154:Aconitate Hydratase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000494:pharmacology*; D019343:Citric Acid / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000201:enzymology*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D019343:Citric Acid; D002784:Cholesterol; D000154:Aconitate Hydratase