Cambios temporales en el metabolismo de glicerofosfolípidos y fosfatidilcolina en cultivos de fibroblastos

ACOSTA, VICTORIA; MARQUEZ SEBASTIAN; SALVADOR, G; GARBARINO PICO, E; GIUSTO, N; GUIDO, M

Buenos Aires

Congreso; V jornadas de Bioquimica y Biologia Molecular de Lipidos y Liporpoteinas; 2012

INIBIBB-INIBIOLP-IQUIFYB

Circadian clocks regulate several  biochemical processes including lipid metabolism and its disruption leads to severe metabolic disorders. Circadian[FC1]  clocks present in immortalized cell lines display daily variations in [32P]-phospholipid labeling; however, little is known about the role of chronobiology  in theregulation of bulk glycerophospholipid (GPL) synthesis. In arrested NIH 3T3 cells synchronized with a 2 h-serum shock, significant temporal variations in: a) the labeling of total [3H]-GPLs, with lowest levels around 28 and 56 h, and b) the activity of GPL-synthesizing and -remodeling enzymes such as phosphatidate phosphohydrolase 1 (PAP-1) and lysophospholipid acyltransferases (LPLAT), respectively, with clear antiphase profiles were observed. In addition, we investigated the temporal regulation of phosphatidylcholine (PC) biosynthesis. PC is mainly synthesized through the Kennedy pathway being Choline Kinase (ChoK) and CTP: phosphocholine cytidylyltranferase (CCT)  key regulatory enzymes. PC labeling exhibited a significant daily variation with lowest levels every ~28 h, variations that were accompanied by brief increases in CCT activity and the oscillation in ChoK mRNA expression and activity. Results demonstrate that synchronized fibroblasts are subject to complex levels of metabolic regulation exhibiting temporal variations in the synthesis of net GPLs and particularly of PC with concerted changes in specific enzyme expression and/or activities.