Kimura T, Chowdhury S, Tanaka T, Shimizu A, Iwase K, Oyadomari S, Gotoh T, Matsuzaki H, Mori M, Akira S, Takiguchi M
Department of Molecular Genetics, Kumamoto University School of Medicine, Japan.
FEBS Lett. 2001 Apr 6;494(1-2):105-11. doi: 10.1016/s0014-5793(01)02320-1.
Transcription of genes for enzymes of the ornithine cycle is activated by hormones such as glucocorticoids and glucagon. Promoters and enhancers of several genes for the enzymes interact with the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors, and C/EBPbeta has been suggested to mediate glucocorticoid response of the gene for arginase, the last enzyme of the cycle. To determine the contribution of C/EBPbeta to hormonal regulation of genes for ornithine cycle enzymes, we examined mice with targeted disruption of the C/EBPbeta gene. Induction of genes for the enzymes by intraperitoneal injection of dexamethasone and glucagon was almost intact in the liver of C/EBPbeta-deficient mice. On the other hand, in primary-cultured hepatocytes derived from C/EBPbeta-deficient mice, induction of genes for the first enzyme carbamylphosphate synthetase, as well as for arginase, in response to dexamethasone and/or glucagon was severely impaired. Therefore, C/EBPbeta is required for hormonal induction of the genes for ornithine cycle enzymes in primary-cultured hepatocytes, while the deficiency of C/EBPbeta is compensated for in vivo.
鸟氨酸循环中酶的基因转录由糖皮质激素和胰高血糖素等激素激活。几种酶基因的启动子和增强子与CCAAT/增强子结合蛋白（C/EBP）转录因子家族相互作用，有人提出C/EBPβ介导精氨酸酶（该循环的最后一种酶）基因的糖皮质激素反应。为了确定C/EBPβ对鸟氨酸循环酶基因激素调节的作用，我们研究了C/EBPβ基因靶向缺失的小鼠。在C/EBPβ缺陷小鼠的肝脏中，通过腹腔注射地塞米松和胰高血糖素诱导酶基因的表达几乎不受影响。另一方面，在源自C/EBPβ缺陷小鼠的原代培养肝细胞中，对去甲肾上腺素和/或胰高血糖素反应时，第一种酶氨基甲酰磷酸合成酶以及精氨酸酶基因的诱导严重受损。因此，C/EBPβ是原代培养肝细胞中鸟氨酸循环酶基因激素诱导所必需的，而C/EBPβ的缺乏在体内得到了补偿。
