Renouf S, Buquet C, Fairand A, Benamar M, Husson A
Groupe de Biochemie Physiopathologie Digestive et Nutritionelle, UFR Médecine-Pharmacie de Rouen, St-Etienne-du-Rouvray, France.
Biochem J. 1993 Apr 15;291 ( Pt 2)(Pt 2):609-13. doi: 10.1042/bj2910609.
During the perinatal period, the activity of the urea-cycle enzyme argininosuccinate lyase (ASL) is regulated by glucocorticoids, glucagon and insulin. In this study, the effects of glucagon and cyclic AMP (cAMP) analogues were examined on the synthesis of ASL and on the level of its corresponding mRNA in cultured foetal hepatocytes. Northern-blot analysis revealed that these agents only gave a transient induction of ASL mRNA amount, which reached a peak at 6 h and declined thereafter. This induction preceded the increase in enzyme activity and amount which could be observed for 2 or 3 days of culture. Stimulation of ASL mRNA accumulation by a combination of cAMP analogues and dexamethasone was additive, indicating that glucocorticoids and cAMP are both necessary to promote hepatocyte differentiation and that inductions could occur via independent pathways. Induction by cAMP analogues could be abolished by actinomycin D, suggesting a control mechanism at the transcriptional level. Puromycin was without effect on ASL mRNA induction by cAMP, indicating that no ongoing protein synthesis was required in the stimulation process.
在围产期，尿素循环酶精氨琥珀酸裂解酶（ASL）的活性受糖皮质激素、胰高血糖素和胰岛素的调节。在本研究中，检测了胰高血糖素和环磷酸腺苷（cAMP）类似物对培养的胎儿肝细胞中ASL合成及其相应mRNA水平的影响。Northern印迹分析显示，这些试剂仅能短暂诱导ASL mRNA量，在6小时达到峰值，随后下降。这种诱导先于酶活性和量的增加，而酶活性和量的增加在培养2或3天后才能观察到。cAMP类似物和地塞米松联合刺激ASL mRNA积累具有相加作用，表明糖皮质激素和cAMP对于促进肝细胞分化都是必需的，且诱导可通过独立途径发生。cAMP类似物的诱导可被放线菌素D消除，提示转录水平的控制机制。嘌呤霉素对cAMP诱导ASL mRNA没有影响，表明刺激过程中不需要正在进行的蛋白质合成。
