Mziaut H, Korza G, Elkahloun A G, Ozols J
Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut 06030-3305, USA.
Biochem Biophys Res Commun. 2001 Apr 13;282(4):910-5. doi: 10.1006/bbrc.2001.4658.
The genes encoding enzymes involved in fatty acid metabolism are regulated by sterols. Stearoyl CoA desaturase, a key enzyme in the synthesis of unsaturated fatty acyl-CoAs is transcriptionally regulated by fat-free diet and sterols. To identify other genes that are induced in rat liver by fat-free diet we performed an in vivo gene expression profile analysis using DNA microarrays. Here we report that among the genes highly expressed is emerin, an integral protein of the inner nuclear membrane. Mutated or nonexpressed emerin occurs in patients with muscular dystrophy. Sterol regulatory element binding proteins activate the transcription of several sterol regulated genes. To investigate whether sterol regulatory element binding proteins or indirectly cholesterol activates the transcription of stearoyl CoA desaturase and emerin, we cultured Chinese hamster ovary (CHO), either in cholesterol-rich or cholesterol-depleted mediums. We also transiently transfected the cell culture with plasmid encoding sterol regulatory element binding proteins in cholesterol-rich medium. Our data show that cholesterol-supplemented media as well as the transient transfection induced the expression of stearoyl CoA desaturase RNA 3.5- and 7-fold respectively. However, the RNA level of emerin was not altered under these conditions, implying that the parallel induction of emerin is independent of the sterol regulatory element binding regulation pathway.
参与脂肪酸代谢的酶的编码基因受固醇调控。硬脂酰辅酶A去饱和酶是不饱和脂肪酰辅酶A合成中的关键酶,其转录受无脂饮食和固醇调控。为了鉴定无脂饮食在大鼠肝脏中诱导表达的其他基因,我们使用DNA微阵列进行了体内基因表达谱分析。在此我们报告,高表达的基因中有核纤层蛋白,它是内核膜的一种整合蛋白。核纤层蛋白发生突变或不表达见于肌营养不良患者。固醇调节元件结合蛋白可激活多个固醇调控基因的转录。为了研究固醇调节元件结合蛋白或间接的胆固醇是否激活硬脂酰辅酶A去饱和酶和核纤层蛋白的转录,我们在富含胆固醇或不含胆固醇的培养基中培养中国仓鼠卵巢(CHO)细胞。我们还在富含胆固醇的培养基中用编码固醇调节元件结合蛋白的质粒对细胞培养物进行瞬时转染。我们的数据表明,添加胆固醇的培养基以及瞬时转染分别使硬脂酰辅酶A去饱和酶RNA的表达增加3.5倍和7倍。然而,在这些条件下核纤层蛋白的RNA水平未改变,这意味着核纤层蛋白的平行诱导独立于固醇调节元件结合调控途径。