Modulation of gene expression by vitamin B6

Abstract

The physiologically active form of vitamin B6, pyridoxal 5'-phosphate (PLP), is known to function as a cofactor in many enzymic reactions in amino acid metabolism. Recent studies have shown that, apart from its role as a coenzyme, PLP acts as a modulator of steroid hormone receptor-mediated gene expression. Specifically, elevation of intracellular PLP leads to a decreased transcriptional response to glucocorticoid hormones, progesterone, androgens, and oestrogens. For example, the induction of cytosolic aspartate aminotransferase (cAspAT) in rat liver by hydrocortisone is suppressed by the administration of pyridoxine. The suppression of the cAspAT induction by pyridoxine is caused by a decrease in the expression of the cAspAT gene, which is brought about by inactivation of the binding activity of the glucocorticoid receptor to the glucocorticoid-responsive element in the regulatory region of the cAspAT gene. Vitamin B6 has recently been found to modulate gene expression not only for steroid hormone-responsive or PLP-dependent enzymes but also for steroid- and PLP-unrelated proteins such as serum albumin. Albumin gene expression was found to be modulated by vitamin B6 through a novel mechanism that involves inactivation of tissue-specific transcription factors, such as HNF-1 or C/EBP, by direct interaction with PLP in a similar manner to glucocorticoid receptor. Enhancement of albumin gene expression in the liver by an increased supply of amino acids can be explained by elevated binding of HNF-1 and C/EBP to their DNA-binding sites which, in turn, is caused by a decrease in the intracellular level of PLP by the increased amino acid supply. These findings that vitamin B6 acts as a physiological modulator of gene expression add a new dimension to the hitherto recognized function of vitamin B6 as a cofactor of enzyme action.

Prediagnostic Plasma Pyridoxal 5′-Phosphate (Vitamin B6) Levels and Invasive Breast Carcinoma Risk: The Multiethnic Cohort

“…The exact mechanism through which vitamin B6 exerts anti-tumorigenic effects is presently unknown (6). Decreased growth of tumor cells by vitamin B6 treatment has been attributed to modulation of steroid hormone receptor-mediated gene expression (34, 37–39). Because steroid hormones are involved in the regulation of cellular growth, differentiation, and maintenance of physiological function, the potential for PLP to modulate these hormones could represent a novel therapeutic approach to the inhibition of breast cancer growth.…”

Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies

“…PLP is the active coenzyme of vitamin B 6 , and is essential for the metabolism, catabolism, and transamination of amino acids [90] as well as several other physiological reactions [13]. It has been suggested that PLP increases the availability of molecules needed for normal metabolic functioning, aids in glycogenolysis [22,135], and reduces excitotoxicity [13,151], all of which are proposed mechanisms for neuroprotective effects.…”

Role of vitamin B6 in idiopathic burning mouth syndrome: some clinical observations

“…In cultured cells, moderate variations in the intracellular concentrations of PLP can have pronounced modulatory effects on steroid-induced gene expression. Specifically, elevation of intracellular PLP levels leads to decreased transcriptional responses to glucocorticoid, progesterone, androgen, or estrogen hormones, suggesting that vitB6 acts as an inhibitor of estrogen action [12,19]. Steroid hormones can accumulate in the nucleus of target tissues for a longer time in case of vitB6 deficiency, leading to enhanced gene expression [18,20].…”