CIRCADIAN CONTROL OF LIPID AND REDOX METABOLISMS IN PROLIFERATIVE CANCER CELLS

MONJES, NATALIA M.; WAGNER, PAULA M.; SOSA-ALDERETE LUCAS; GUIDO, MARIO E.

Córdoba

Congreso; SAN, Sociedad Argentina de investigaciones en Neurociencias; 2018

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). Circadian rhythm disruption may cause higher cancer risk; but, little is known about clock function in tumor cells. Recently we worked with cultures of glioblastoma T98G cells as tumoral model to evaluate the circadian, redox and metabolic state. In arrested cells we observed functional and rhythmic clock oscillations in: mRNA for clock genes (CGs) and glycerophospholipid (GPL) enzyme genes; 32P-GPL labeling and redox state/peroxiredoxin oxidation cycles. Nevertheless, in proliferating cells circadian rhythms of gene expression were affected whereas the metabolic rhythms persist (fig. 1,2 and 4). Moreover redox state rhythms were altered when Bmal1 expression was knocked down (fig. 3). Thus metabolic clock operates in proliferative tumor cells regardless the molecular clock. On the other hand we expanded this study to a different tumoral model to assess the generality of that effects. We worked with the human hepatoma cell line HepG2 to assess the molecular clock work and its linkage with the lipid metabolism under proliferation. We analyzed the expression and protein content of CGs, clock controlled genes (CCGs) and enzymes involved in the GPL biosynthesis (fig. 5). We also studied the endogenous phospholipid content, the individual level of lipids (fig. 6) and the lipid droplet content: number, size and area variation per cell over time (fig. 7). We found an active timedependent control of gene expression and metabolism in proliferating HepG2 cells.