Zolfaghari R, Ross A C
Department of Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
J Lipid Res. 1994 Nov;35(11):1985-92.
Apolipoprotein A-I (apoA-I) gene expression is known to be regulated by nutritional and hormonal factors. Experiments were conducted to determine the effects of vitamin A deficiency and retinoic acid repletion on the in vivo expression of apoA-I in rat intestine and liver. The relative abundance of apoA-I mRNA (apoA-I/beta-actin ratio) in the intestine did not differ significantly between vitamin A-deficient and -sufficient rats. However, the relative abundance of hepatic apoA-I mRNA of vitamin A-deficient rats was 2.2- to 6-times that of sufficient rats. Even marginal vitamin A status resulted in a significant increase in hepatic apoA-I mRNA expression. Treatment of vitamin A-deficient rats with a single dose of retinoic acid (20 micrograms, 20 h before tissues were collected) reduced the hepatic apoA-I mRNA/beta-actin ratio by about 40%, while further reduction (about 60-65%) was observed after two treatments with retinoic acid. By nuclear run-on assay, the increase in hepatic apoA-I mRNA in vitamin A-deficient rats was attributable to increased transcription of the apoA-I gene. However, immunoblot analysis showed no apparent differences in apoA-I protein in either liver homogenates or plasma of vitamin A-deficient and -sufficient rats. These data indicate that apoA-I gene expression in vivo is sensitive to retinoid status and suggest that there is additional regulation of post-transcriptional events.
已知载脂蛋白A-I(apoA-I)基因表达受营养和激素因素调控。开展实验以确定维生素A缺乏和视黄酸补充对大鼠肠道和肝脏中apoA-I体内表达的影响。维生素A缺乏和充足的大鼠肠道中apoA-I mRNA的相对丰度(apoA-I/β-肌动蛋白比值)无显著差异。然而,维生素A缺乏大鼠肝脏中apoA-I mRNA的相对丰度是充足大鼠的2.2至6倍。即使是边缘性维生素A状态也会导致肝脏中apoA-I mRNA表达显著增加。用单剂量视黄酸(20微克,在收集组织前20小时)处理维生素A缺乏大鼠,可使肝脏中apoA-I mRNA/β-肌动蛋白比值降低约40%,而视黄酸两次处理后进一步降低(约60-65%)。通过核转录分析,维生素A缺乏大鼠肝脏中apoA-I mRNA的增加归因于apoA-I基因转录增加。然而,免疫印迹分析显示,维生素A缺乏和充足大鼠的肝脏匀浆或血浆中apoA-I蛋白无明显差异。这些数据表明,体内apoA-I基因表达对视黄醇状态敏感,并提示转录后事件存在额外调控。