T. Oka et al., VITAMIN-B-6 MODULATES EXPRESSION OF ALBUMIN GENE BY INACTIVATING TISSUE-SPECIFIC DNA-BINDING PROTEIN IN RAT-LIVER, Biochemical journal, 309, 1995, pp. 243-248
The level of albumin mRNA in the liver of vitamin B-6-deficient rats w
as found to be 7-fold higher than that of control rats. Since the tran
scriptional activity of the albumin gene, as measured by a nuclear run
-on assay, was increased 5-fold in vitamin B-6 deficiency, the higher
concentration of albumin mRNA in the liver of vitamin-deficient rats c
ould be attributed to the enhanced rate of transcription. The promoter
proximal sequences of the albumin gene interact with a number of tiss
ue-specific transcription factors including HNF-1 and C/EBP. We determ
ined the binding activities of liver nuclear extracts to the HNF-1- an
d C/EBP-binding sites by gel mobility-shift assay and found that the a
ctivities of the extract prepared from liver of vitamin B-6-deficient
rats were greater than those of controls. As the concentrations of C/E
BP in nuclear extracts from control and vitamin-deficient rats, estima
ted by Western-blot analysis, were essentially the same, the lower bin
ding activity of the extract from control liver is probably due to ina
ctivation of tissue-specific factors by pyridoxal phosphate and/or its
analogues. We therefore examined the effect of pyridoxal phosphate an
d its analogues on the binding activity of nuclear extract in vitro an
d found that only pyridoxal phosphate effectively inhibited the bindin
g. These observations indicate that vitamin B-6 modulates albumin gene
expression through a novel mechanism that involves inactivation of ti
ssue-specific transcription factors by direct interaction with pyridox
al phosphate.