Feng Tsui-Hsia, Tsui Ke-Hung, Juang Horng-Heng
Department of Nursing, Chang Gung University Tao-Yuan, Taiwan, ROC.
Chin J Physiol. 2005 Jun 30;48(2):93-100.
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.
线粒体乌头酸酶（mACON）是线粒体三羧酸循环中柠檬酸氧化的关键酶。用胆固醇（10微克/毫升胆固醇和1微克/毫升25-羟基胆固醇）处理24小时可刺激人前列腺癌细胞（PC-3）和肝癌细胞（HepG2）中的mACON酶活性。胆固醇合成拮抗剂美伐他汀可阻断胆固醇处理对mACON的影响。胆固醇处理刺激了mACON酶活性，这增强了PC-3细胞中柠檬酸的利用，但降低了细胞内ATP水平。免疫印迹和瞬时基因表达分析表明，胆固醇处理可增强mACON的基因表达。将假定的固醇反应元件（SRE）从GACGCCCCACT突变为GACGCCCATAT可消除胆固醇对mACON基因启动子活性的刺激作用。结果表明，胆固醇处理通过SRE信号转导途径诱导mACON基因表达。我们的研究证明了胆固醇对柠檬酸代谢的失调作用。
