CCAAT/enhancer‐binding protein β is required for activation of genes for ornithine cycle enzymes by glucocorticoids and glucagon in primary‐cultured hepatocytes

FEBS Letters

Kimura, Tatsuya⁴  Iwase, Katsuro⁴  Matsuzaki, Hiromitsu¹  Takiguchi, Masaki⁴  Chowdhury, Shoaib⁴  Oyadomari, Seiichi⁴  Gotoh, Tomomi⁴  Shimizu, Atsuko²  Tanaka, Takashi³  Akira, Shizuo³  Mori, Masataka⁴ 

[1]Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan

[2]Department of Biochemistry, Chiba University School of Medicine, Inohana 1-8-1, Chiba 260-8670, Japan

[3]Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan

[4]Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan

关键词: Transcription factor;    Gene regulation;    Hormone;    Dexamethasone;    Gene targeting;    Knockout mouse;    CPS;    carbamylphosphate synthetase;    OTC;    ornithine transcarbamylase;    AS;    argininosuccinate synthetase;    AL;    argininosuccinate lyase;    C/EBP;    CCAAT/enhancer-binding protein;    MT;    metallothionein;    TAT;    tyrosine aminotransferase;    PEPCK;    phosphoenolpyruvate carboxykinase;    GR;    glucocorticoid receptor;   

DOI  :  10.1016/S0014-5793(01)02320-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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/EBPβ has been suggested to mediate glucocorticoid response of the gene for arginase, the last enzyme of the cycle. To determine the contribution of C/EBPβ to hormonal regulation of genes for ornithine cycle enzymes, we examined mice with targeted disruption of the C/EBPβ gene. Induction of genes for the enzymes by intraperitoneal injection of dexamethasone and glucagon was almost intact in the liver of C/EBPβ-deficient mice. On the other hand, in primary-cultured hepatocytes derived from C/EBPβ-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/EBPβ is required for hormonal induction of the genes for ornithine cycle enzymes in primary-cultured hepatocytes, while the deficiency of C/EBPβ is compensated for in vivo.

【 授权许可】

Unknown