期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 398, 期 1, 页码 79-86出版社
ELSEVIER SCIENCE INC
DOI: 10.1006/abbi.2001.2713
关键词
human aldehyde dehydrogenase 2 promoter; hepatocyte nuclear factor 4; cyclic AMP; COUP transcription factors, fasting
资金
- NIAAA NIH HHS [AA07611, AA06463] Funding Source: Medline
An important regulatory element (designated FP330-3') of the ALDH2 Promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARdelta suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3' by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3'. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting. (C) 2002 Elsevier Science.
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