LACK OF TNFRp55 MODIFIES TEMPORAL PATTERNS OF CHOLESTEROL REGULATION-RELATED PROTEINS IN THE LIVER

RAGUSA JAV; ARIAS JL; ALTAMIRANO FG; DE LA VEGA M; CASAIS M; ANZULOVICH AC

Congreso; XXXII Reunión Anual de la Soc. de Biología de Cuyo; 2014

HDL-associated ApoE is the main cholesterol carrier into mice steroidogenic tissues. On the other hand, RAR/RXR heterodimer induces the expression of the cholesterol catabolizing enzyme in the liver. There is evidence that cholesterol metabolism is regulated by the circadian clock and TNF has been proposed as a modulator of circadian rhythms. In this work, our objective was to evaluate the consequences of TNF receptor p55 deficiency on the 24h-patterns of three cholesterol regulation-related proteins, ApoE, RXRα and RARα. Female C57BL/6 wild type (WT) and TNFRp55-/- (KO) mice were maintained on a 12-h light: 12-h dark cycle, at 24±2°C, with irradiated food and water available ad-libitum. Five days before the experiment mice were kept under constant darkness conditions. Liver samples were obtained every 6 h during a 24h period. Specific protein levels were analyzed by Western-blot. TNFRp55-deficient mice did not show differences in the ApoE temporal expression in liver, in comparison to the WT group. However, 24h-rhythms of RXR and RAR protein levels were phase shifted in the liver of KO mice. Thus, we suggest TNF, through its p55 receptor signaling pathway, could play a role in the modulation of temporal profiles of proteins involved in cholesterol homeostasis in the liver, a peripheral clock with relevant function in metabolism.