A metabolic circadian clock controls rhythms in immortalized human glioblastoma T98G cells

WAGNER PAULA; LUCAS G. SOSA-ALDERETE; LUCAS GORNÉ

Congreso; Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2016

Circadian clocks present even in immortalized cell lines temporarily regulate diverse physiological processes and can be synchronized by different ambient signals. The disruption of circadian rhythms may lead to metabolic disorders or higher cancer risk through failures in cell division control. Previous results in immortalized human glioblastoma T98G cells showed that clock genes (Bmal1, Per1, Rev-Erbα), some phospholipid (PL) synthesizing enzyme genes and the labelling of 32P-PLs exhibited different temporal profiles depending on the growth condition tested (proliferation: P, partial arrest: A) with metabolic rhythms mainly preserved under P.Here we evaluated redox metabolism (redox state and peroxiredoxin oxidation cycles) and the activities of PL synthesizing enzymes for phosphatidate phosphohydrolase (PAP) and lysophospholipid acyl transferases (LPLAT) in T98G cells under P or A, synchronized with dexamethasone (100 nM) (time 0) and collected at different times for 36 h. Results showed that redox state, peroxiredoxin oxidation cycles and PAP activity exhibited temporal oscillations in both growth conditions tested (P & A) while LPLAT activity seems to be rhythmic under P. Our observations support the idea that a metabolic clock could operate in these tumor cells regardless the molecular clock which was not found to work properly under proliferation.