Circadian Variation Of Glutathione Metabolism Is Modified In The Vitamin A Deficiency

PONCE, I. T.; REZZA, I. G.; BONOMI M.R.; DELGADO, S. M.; GIMÉNEZ MS; ANZULOVICH A.C.

Mar del Plata, Bs. As.

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

SAIB

Glutathione (GSH) is essential for the maintenance of an optimal cellular redox state and the production of NADPH+H+, which are critical for the transcriptional activity of the biological clock. Retinoid receptor binding sites and E-box sites have been found in the regulatory regions of Glutathione Peroxidase (GPx) and Glutathione reductase (GR) genes. Our objective was to investigate the daily variation of RARs, RXRs, GPx and GR mRNA levels as well as GR activity and GSH levels in the liver of control, vitamin A-deficient and vitamin A-recovered rats. Liver total RNA was extracted using the Trizol reagent (Invitrogen). Transcript levels of RARalpha, RXRalpha, RXRbeta, GPx and GR were determined by RT-PCR and normalized to β-actin as endogenous control. GR activity and GSH levels were determined following Schaedle & Bassham (1977) and Akerboon & Sies (1981), respectively. Interestingly, we observed a daily rhythmicity in the expression of RXRalpha and beta, GPx and GR activity as well as in the GSH levels which were differentially modified by the vitamin A deficiency. Circadian regulation of glutathione metabolism and cellular redox state could be mediated, directly or indirectly, by retinoids receptors. This work was supported by NIH Res.Grant R01-TW006974 funded by the FIC, USA.