Hillgartner F B, Charron T, Chesnut K A
Department of Biochemistry, School of Medicine, West Virginia University, Morgantown 26506, USA.
Arch Biochem Biophys. 1997 Jan 15;337(2):159-68. doi: 10.1006/abbi.1996.9776.
The mechanisms by which triiodothyronine (T3), glucose, insulin, and glucagon regulate acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes have been investigated. Incubating hepatocytes with T3 in the absence of glucose caused a fourfold increase in acetyl-CoA carboxylase activity. Addition of glucose (20 mM) enhanced the T3-induced increase in acetyl-CoA carboxylase activity by threefold but had no effect on enzyme activity in the absence of T3. The effects of T3 and glucose on acetyl-CoA carboxylase activity were accompanied by similar changes in acetyl-CoA carboxylase mRNA levels, indicating that regulation occurred at a pretranslational step. Xylitol mimicked the effect of glucose on acetyl-CoA carboxylase mRNA abundance, suggesting that an intermediate(s) of the nonoxidative branch of the pentose phosphate pathway may be involved in mediating this response. Insulin accelerated the accumulation of acetyl-CoA carboxylase mRNA abundance caused by T3 and glucose but had no effect on steady-state levels of acetyl-CoA carboxylase mRNA in the absence or presence of T3. Glucagon caused a 65% decrease in the accumulation of acetyl-CoA carboxylase mRNA in hepatocytes incubated with T3 and glucose. The effects of T3, glucose, insulin, and glucagon on the abundance of acetyl-CoA carboxylase mRNA were accounted for by changes in the transcription rate of the acetyl-CoA carboxylase gene. These data support the hypothesis that T3, glucose, insulin, and glucagon play a role in mediating the effects of nutritional manipulation on transcription of acetyl-CoA carboxylase in liver.
已对三碘甲状腺原氨酸（T3）、葡萄糖、胰岛素和胰高血糖素在鸡胚肝细胞原代培养物中调节乙酰辅酶A羧化酶表达的机制进行了研究。在无葡萄糖的情况下用T3孵育肝细胞，可使乙酰辅酶A羧化酶活性增加四倍。添加葡萄糖（20 mM）可使T3诱导的乙酰辅酶A羧化酶活性增加进一步提高三倍，但在无T3时对酶活性无影响。T3和葡萄糖对乙酰辅酶A羧化酶活性的影响伴随着乙酰辅酶A羧化酶mRNA水平的类似变化，表明调节发生在翻译前步骤。木糖醇模拟了葡萄糖对乙酰辅酶A羧化酶mRNA丰度的影响，提示磷酸戊糖途径非氧化分支的一种或多种中间产物可能参与介导此反应。胰岛素加速了由T3和葡萄糖引起的乙酰辅酶A羧化酶mRNA丰度的积累，但在无T3或有T3时对乙酰辅酶A羧化酶mRNA的稳态水平均无影响。胰高血糖素使在T3和葡萄糖孵育的肝细胞中乙酰辅酶A羧化酶mRNA的积累减少65%。T3、葡萄糖、胰岛素和胰高血糖素对乙酰辅酶A羧化酶mRNA丰度的影响是由乙酰辅酶A羧化酶基因转录速率的变化引起的。这些数据支持以下假说：T3、葡萄糖、胰岛素和胰高血糖素在介导营养调控对肝脏中乙酰辅酶A羧化酶转录的影响方面发挥作用。
