Daily oscillation of glutathione redox cycle is dampened in the nutritional vitamin A deficiency

Examples of hormonal phase-shifting of circadian gene expression began to emerge a few years ago. Vitamin A fulfills a hormonal function by binding of retinoic acid to its nuclear receptors, RARs and RXRs. We found retinoid- as well as clock-responsive sites on regulatory regions of Glutathione reductase (GR) and Glutathione peroxidase (GPx) genes. Interestingly, we observed retinoid receptors, as well as GSH, GR, and GPx, display daily oscillating patterns in the rat liver. We also found that feeding animals with a vitamin A-free diet, dampened daily rhythms of RAR alpha and RXR beta mRNA, GR expression and activity, GSH, BMAL1 protein levels, and locomotor activity. Differently, day-night oscillations of RXR alpha, GPx mRNA levels and activity and PER1 protein levels, were phase-shifted in the liver of vitamin A-deficient rats. These observations would emphasize the importance of micronutrient vitamin A in the modulation of biological rhythms of GSH and cellular redox state in liver.