文章基本信息

标题：Pyridoxal 5'-Phosphate Modulates Expression of Cytosolic Aspartate Aminotransferase Gene by Inactivation of Glucocorticoid Receptor
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作者：Tatsuzo OKA ; Naomi KOMORI ; Masashi KUWAHATA 等
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：1995
卷号：41
期号：3
页码：363-375
DOI：10.3177/jnsv.41.363
出版社：Center for Academic Publications Japan
摘要：The level of mRNA for cytosolic aspartate aminotransfer-ase (cAST) in the liver of vitamin B₆-deficient rats was found to be 7-fold higher than that of the control rats. The administration of hydrocortisone to adrenalectomized vitamin B₆-deficient rats induced expression of hepat-ic cAST mRNA and the induction was suppressed by the simultaneous administration of pyridoxine. Since the 5' regulatory region of the rat cAST gene contains several sequences showing homology to glucocorti-coid-responsive elements, we synthesized an oligonucleotide probe of glucocorticoid-responsive element sequence and assayed the binding activ-ity of liver nuclear extract to the oligonucleotide by gel mobility shift analysis. We found that the binding activity of nuclear extract prepared from the liver of vitamin B₆-deficient rats was far greater than that of the control rats, indicating that the DNA-binding activity of glucocorticoid receptor was enhanced by vitamin B₆ deficiency. We further 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 glucocorticoid-responsive element. Con-geners of pyridoxal phosphate, such as pyridoxamine 5'-phosphate, pyri-doxal, pyridoxamine and pyridoxine, did not show 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 elements.
关键词：vitamin B6;aspartate aminotransferase;gene expression;glucocorticoid receptor;glucocorticoid-responsive element;rats