Circadian clock expression is modified in the liver of vitamin a-deficient rats.

PONCE IT; REZZA IG; GOLINI RS; DELGADO SM; ANZULOVICH AC

San Miguel deTucuman, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

SAIB

Mammalian liver has its own cellular clock machinery which controls and synchronizes circadian gene expression. Previously, we showed RARa, RXRa and RXRa expression display a daily rhythmicity in the rat liver. Our objective was to investigate whether vitamin A deficiency modifies circadian expression of clock genes in the rat liver, by modifying retinoid receptors daily oscillation. Holtzman rats weaned at 21 d of age were assigned to either the experimental diet, devoid of vitamin A (vitamin Adeficient group) or the same diet containing 4000 IU of vitamin A/Kg diet (control group) during 3 months. Liver samples were taken every 4 h. Total RNA was extracted using the Trizol reagent. Transcript levels of Bmal1, Per1, Cry1 and RevErbb were determined by RT-PCR. Protein levels were analyzed by immunoblotting. Regulatory regions of clock genes were scanned for retinoid receptors binding sites using the MatInspector software (www.genomatix.de). We observed daily rhythmicity of clock - gene and protein- expression were differentially modified in the liver of vitamin A-deficient rats, probably, as a consequence of temporal changes in RAR and RXR expression. Thus, vitamin A might be essential to establish circadian clock expression in the liver, a peripheral clock with a relevant function in daily metabolism. This work has been supported by NIH Grant R01-TW006974 funded by the FIC, USA.