Alterations in the DNA binding activity of transcriptional factors activator protein-1, Sp1, and hepatocyte nuclear factor-1 in rat jejunum during starvation and refeeding.
BACKGROUND
The molecular processes leading to mucosal atrophy, regrowth, and functional changes with starvation and refeeding are largely unknown. There are many transcriptional factors that might be related to mucosal atrophy and proliferation. In contrast, we previously reported that H+/peptide transporter and aminopeptidase N messenger RNA in the intestinal mucosa were upregulated during starvation. Therefore, we selected and studied three transcriptional factors: activator protein (AP)-1, Sp1, and hepatocyte nuclear factor (HNF)-1, which not only play important roles for enterocytes proliferation, but also exist in promoter lesions of the brush border enzymes and peptide transporter.


METHODS
In the present study, we performed electrophoretic mobility shift assays employing AP-1, Sp1, and HNF-1, and evaluated the changes in the DNA binding activities in rat jejunum during starvation and refeeding.


RESULTS
Two days after starvation, the Sp1 binding activity was significantly decreased to 61.8% as compared with the control level, whereas AP-1 was 121.4% and HNF-1 was 77.5%. Two hours after refeeding, the AP-1 activity was significantly increased to 175.0% as compared with the control level, and the HNF-1 activity was significantly increased to 180.2%. In contrast, the decreased SP1 level did not recover until 24 h after refeeding.


CONCLUSIONS
The DNA binding activities of these three transcriptional factors were significantly changed in the rat jejunum during starvation and refeeding. Our results provide insight into the molecular mechanisms of the transcriptional regulations associated with mucosal atrophy, regrowth, and functional changes of the jejunal epithelium in response to starvation and refeeding.
Ihara
Takashi
T
Division of Gastroenterology and Vice President, Shiga University of Medical Science, Seta, Otsu, Japan.
Tsujikawa
Tomoyuki
T
Fujiyama
Yoshihide
Y
Bamba
Tadao
T
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003720:Densitometry; D004435:Eating / Q000502:physiology*; D004586:Electrophoresis; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta