Kawabe Y, Honda M, Wada Y, Yazaki Y, Suzuki T, Ohba Y, Nabata H, Endo A, Matsumoto A, Itakura H
Third Department of Internal Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1994 Aug 15;202(3):1460-7. doi: 10.1006/bbrc.1994.2095.
Under conditions of cholesterol depletion and SREBP-1 accumulation, changes in the levels of sterol regulatory element binding protein(s) (SREBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipoprotein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also increased by the cholesterol depletion. In contrast, levels for SREBP-1a and 1b (1a/b) mRNA increased transiently and then decreased. To examine the effect of SREBP-1 accumulation, Hep G2 cells were incubated with a SREBP-1 degradation inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN). The ALLN treatment increased the LDL receptor mRNA significantly, and also increased mRNA levels for HMG-CoA reductase, SREBP-1a/b and SREBP-2. The mRNA level for squalene synthase was not changed, and for SREBP-1c was decreased by the treatment. In conclusion, the regulation of differential expression of SREBP mRNA may be involved in sterol mediated regulation of gene expression. Moreover, the regulation of the SREBP-1 level may be a critical step in the regulation of sterol mediated LDL receptor expression.
在胆固醇耗竭和SREBP - 1积累的条件下，通过核糖核酸酶保护试验研究了Hep G2细胞中固醇调节元件结合蛋白（SREBPs）水平和固醇调节基因mRNA的变化。胆固醇耗竭增加了胆固醇生物合成酶和低密度脂蛋白（LDL）受体的mRNA表达。胆固醇耗竭也使SREBP - 1c和SREBP - 2的mRNA水平升高。相比之下，SREBP - 1a和1b（1a/b）mRNA水平先短暂升高然后下降。为了研究SREBP - 1积累的影响，将Hep G2细胞与SREBP - 1降解抑制剂N - 乙酰 - 亮氨酰 - 亮氨酰 - 正亮氨酸（ALLN）一起孵育。ALLN处理显著增加了LDL受体mRNA水平，同时也增加了HMG - CoA还原酶、SREBP - 1a/b和SREBP - 2的mRNA水平。鲨烯合酶的mRNA水平没有变化，而SREBP - 1c的mRNA水平在处理后下降。总之，SREBP mRNA差异表达的调节可能参与了固醇介导的基因表达调节。此外，SREBP - 1水平的调节可能是固醇介导的LDL受体表达调节中的关键步骤。
