T. Oka et al., PYRIDOXAL 5'-PHOSPHATE MODULATES EXPRESSION OF CYTOSOLIC ASPARTATE-AMINOTRANSFERASE GENE BY INACTIVATION OF GLUCOCORTICOID RECEPTOR, Journal of nutritional science and vitaminology, 41(3), 1995, pp. 363-375
The level of mRNA for cytosolic aspartate aminotransferase (cAST) in t
he liver of vitamin B-6-deficient rats was found to be 7-fold higher t
han that of the control rats. The administration of hydrocortisone to
adrenalectomized vitamin B-6-deficient rats induced expression of hepa
tic cAST mRNA and the induction was suppressed by the simultaneous adm
inistration of pyridoxine. Since the 5' regulatory region of the rat c
AST gene contains several. sequences showing homology to glucocorticoi
d-responsive elements, we synthesized an oligonucleotide probe of gluc
ocorticoid-responsive element sequence and assayed the binding activit
y of liver nuclear extract to the oligonucleotide by gel mobility shif
t analysis. We found that the binding activity of nuclear extract prep
ared from the liver of vitamin B-6-deficient rats was far greater than
that of the control rats, indicating that the DNA-binding activity of
glucocorticoid receptor was enhanced by vitamin B-6 deficiency. We fu
rther found that preincubation of the nuclear extract from the vitamin
-deficient liver with pyridoxal 5'-phosphate brought about a rapid and
extensive decrease in the binding of the extract to the glucocorticoi
d-responsive element. Congeners of pyridoxal phosphate, such as pyrido
xamine 5'-phosphate, pyridoxal, pyridoxamine and pyridoxine, did not s
how an inhibitory effect. These observations suggest that pyridoxal 5'
-phosphate modulates cAST gene expression by inactivating the binding
activity of glucocorticoid receptor to glucocorticoid-responsive eleme
nts.