Modulation of albumin gene expression by amino acid supply in rat liver is mediated through intracellular concentration of pyridoxal 5′-phosphate

Abstract

Rats were nourished by infusion of total parenteral nutrition solutions containing 0% or 3.3% amino acids for 7 days. The level of albumin mRNA in the liver of amino acid-infused rats was found to be several fold higher than that in the liver of amino acid-depleted rats. Expression of albumin gene is known to be regulated by tissue-specific transcription factors such as HNF-1 and C EBP . We determined the binding activities of liver nuclear extracts to the HNF-1- and C EBP -binding sites by gel mobility-shift assay and found that the activities of the extract prepared from liver of amino acid-infused rats were greater than those of amino acid-depleted rats. In view of our recent finding that vitamin B 6 modulates albumin gene expression through inactivation of tissue-specific transcription factors by direct interaction with pyridoxal phosphate, we determined the intracellular concentrations of vitamin B 6 derivatives. We found that the concentration of pyridoxal phosphate in the liver of amino acid-infused rats was decreased to almost half of that of amino acid-depleted rats, whereas the concentration of pyridoxamine phosphate was increased in the opposite direction. These observations suggest that an increase in albumin mRNA level in the liver of amino acid-infused rats may be caused by a decrease in intracellular concentration of pyridoxal phosphate, which in turn relieves inactivation of tissue-specific transcription factors.