Gomez P F, Ito K, Huang Y, Otsu K, Kuzumaki T, Ishikawa K
Department of Biochemistry, Yamagata University School of Medicine, Japan.
Arch Biochem Biophys. 1994 Nov 1;314(2):307-14. doi: 10.1006/abbi.1994.1447.
In the liver of the fasted rat, the aldolase B (AldB) mRNA level decreased to about half of that of the control rat. When the control rat was refed the glucose-rich diet, the AldB mRNA level increased about six to seven times more than in the fasted rat. This increase was shown as the activation of the AldB gene transcription by a nuclear run-on assay. To understand the causal factor(s) for this activation, the relationship between the AldB mRNA level in the liver and the plasma concentrations of hormones, which are known as major regulators of carbohydrate metabolism during fasting and refeeding, was investigated. The plasma insulin level in the rat which was refed the glucose-rich diet increased in parallel to AldB mRNA level, while the plasma glucagon level decreased reciprocally to it. The relationship of the plasma corticosterone level to the AldB mRNA level was not obvious. To directly confirm the effects of these hormones on AldB gene transcription in the liver, the responses of AldB gene in the primary cultured hepatocytes to these hormones were examined. Insulin and dexamethasone were effective to activate AldB gene, while glucagon and thyroxine were suppressive. Thyroxine did not extinguish the effects of insulin and dexamethasone, but glucagon canceled them. Thus, it is probable that in vivo these hormones synergistically regulate the AldB gene transcription. In vitro transcription analysis of two AldB promoter constructs suggested that the proximal half of the AldB promoter (up to -92 bp from the transcription start site) is, at least in part, involved for this induction, and the distal half which contains liver-specific elements (-93 to -202 bp) is not involved. The possible explanation for the dietary regulation of aldolase B gene transcription in the liver is discussed.
在禁食大鼠的肝脏中，醛缩酶B（AldB）的mRNA水平降至对照大鼠的约一半。当给对照大鼠重新喂食富含葡萄糖的饮食时，AldB的mRNA水平比禁食大鼠增加了约六至七倍。通过核转录分析表明这种增加是由于AldB基因转录的激活。为了了解这种激活的因果因素，研究了肝脏中AldB mRNA水平与激素血浆浓度之间的关系，这些激素是禁食和重新喂食期间碳水化合物代谢的主要调节因子。重新喂食富含葡萄糖饮食的大鼠的血浆胰岛素水平与AldB mRNA水平平行升高，而血浆胰高血糖素水平则与之呈相反下降。血浆皮质酮水平与AldB mRNA水平的关系不明显。为了直接证实这些激素对肝脏中AldB基因转录的影响，检测了原代培养肝细胞中AldB基因对这些激素的反应。胰岛素和地塞米松可有效激活AldB基因，而胰高血糖素和甲状腺素则具有抑制作用。甲状腺素并未消除胰岛素和地塞米松的作用，但胰高血糖素抵消了它们的作用。因此，在体内这些激素可能协同调节AldB基因转录。对两种AldB启动子构建体的体外转录分析表明，AldB启动子的近端一半（从转录起始位点起至-92 bp）至少部分参与了这种诱导，而包含肝脏特异性元件的远端一半（-93至-202 bp）则未参与。本文讨论了肝脏中醛缩酶B基因转录的饮食调节的可能解释。
