Gamma aminobutyric acid increases erythropoietin overexpression of hypoxia inducible factors in rats

In this study, we investigated the effect of γ-aminobutyric acid (GABA) on serum EPO level and erythropoiesis, and its mechanism was elucidated in rat. GABA significantly (P < 0.05) increased EPO level in serum and expression levels of EPO and EPOR in a dose dependent manner. GABA increased the expression levels of HIF-1 and HIF-2 in a dose dependent manner compared with the negative control; while GABA did not affect the expression of prolyl-hydroxylase domain protein-2α (PHD-2α) gene, an oxygen sensor. GABA supplementation alters energy production pathway resulted in hypoxic condition, which increases EPO level in rat through overexpression of HIF-1 and HIF-2. This study shows a new physiological role of GABA in EPO production and thus GABA could contribute to the prevention of anemia by using alone or in combination with other anemia treating drugs.