The metabolism of phospholipids oscillates rhythmically in cultures of fibroblasts and is regulated by the clock protein PERIOD 1

SEBASTIAN MARQUEZ, PILAR CRESPO, VALERIA CARLINI, EDUARDO GARBARINO-PICO, RUBEN BALER, BEATRIZ L. CAPUTTO, AND MARIO E. GUIDO

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Año: 2004 vol. 18 p. 519 - 521

0892-6638

ABSTRACT The  mammalian  circadian  timing  system  is  composed  of  countless  cell  oscillators distributed throughout  the  body  and  central  pacemakers  regulating  temporal  physiology  and  behavior. Peripheral clocks display circadian rhythms in gene expression both in vivo and in culture. We examined the biosynthesis of phospholipids as well as the expression of the clock gene period 1 (Per1) and its potential involvement in the regulation of the phospholipid metabolism in cultured quiescent  NIH  3T3  cells  synchronized  by  a  2  h  serum shock. A 30 min pulse of radiolabeled precursor was given at phases ranging from 0.5 to  62  h  after serum  treatment. We  observed  a daily  rhythm  in  the  phospholipid  labeling  that  persisted  at  least  for  two  cycles,  with  levels significantly decreasing 29  and  58  h  after  treatment.  Per1 expression exhibited a rapid and transient  induction  and  a  daily  rhythmicity  in  antiphase  to  the  lipid  labeling.  After  Per1 expression knockdown, the rhythm of phospholipid labeling was lost. Furthermore, in cultures of CLOCK  mutant  fibroblasts—cells  with  a  clock  mechanism  impairment—PER1  was  equally expressed  at  all  times  examined  and  the  phospholipid  labeling  did  not  oscillate.  The  results demonstrate that the biosynthesis of phospholipids oscillates daily in cultured fibroblasts by an endogenous clock mechanism involving Per1 expression.