Studies on the molecular clock and the circadian regulation of hepatic tumoral cell metabolism

MONJES NATALIA MARIBEL; GUIDO MARIO EDUARDO

Córdoba

Congreso; SAIB-Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

The circadian system comprising oscillators present in organs, tissues and even in individual cells temporally controls the body physiology. At the molecular level the ?clock genes? (CGs) regulate their own expression and that of others ?clock controlled genes? (CCGs). The clock liver controls the metabolism under a circadian base depending on feeding times; however, it is still unknown how liver works under a malignant growth. The aim of this project was to investigate the molecular clock work and the regulation of genes involved in the lipid metabolism in cultures of the human hepatoma cell line HepG2. We performed this study under two proliferative states, partial arrest and proliferation, maintaining cells with 0 or 5% of serum respectively after synchronization with dexamethasone (100 nM). We analyzed the expression of CGs (Bmal, Per, Cry), CCGs (Rev-erb) and the main enzymes involved in the glycerophospholipids (GPLs) biosynthesis (Chk, Pcyt) by qPCR. All genes assessed except Chkshowed oscillations under proliferation while no differences were observed in arrested cells except forPcyt2. When we studied the endogenous content of GPLs in proliferation, we observed significant variations in the global and individual GPL levels at different times. These studies suggest that an active circadian control of metabolism takes place in proliferating HepG2 cells.