INSIBIO   05451
INSTITUTO SUPERIOR DE INVESTIGACIONES BIOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Metabolism of low density lipoprotein-associated phosphatidylcholine in primary hepatocytes
Autor/es:
MINAHK C; KIM KW; NELSON R; TRIGATTI B; LEHNER R; VANCE D
Lugar:
Tafí del Valle, Tucumán
Reunión:
Jornada; XXV Jornadas Científicas Asociación de Biología de Tucumán; 2008
Institución organizadora:
Asociación de Biología de Tucumán
Resumen:
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We have studied the uptake and metabolism of phosphatidylcholine (PC),
the major phospholipid of low density lipoproteins (LDL), by cultures of
primary hepatocytes. Strikingly, in the absence of the LDL receptor, PC
incorporation into hepatocytes was inhibited by only 30%, whereas cholesteryl
ether uptake was inhibited by 60-70%. On the other hand, scavenger receptor
class B, type I, the other important receptor for LDL in the liver, was found
to be responsible for the uptake of the remaining 30-40% of LDL-cholesteryl
ether. PC uptake was, however, only partially inhibited (30%) in scavenger
receptor class B, type I, knock-out hepatocytes.
Once LDL-PC was taken up by hepatocytes, 50% of LDL-[3H]oleate-PC
was converted to triacylglycerol rather than degraded in lysosomes as occurs
for LDL-derived cholesteryl esters. The remainder of the LDL-derived PC was not
significantly metabolized to other products.
Triacylglycerol synthesis from LDL-PC requires a PC-phospholipase C
activity as demonstrated by inhibition with the phospholipase C inhibitor D609
or activation with rattlesnake venom. Small interfering RNA-mediated
suppression of acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2), but not
DGAT1, decreased the acylation of the LDL-derived diacylglycerol.
These findings show that PC in LDL particles is taken up not only by the
classical receptors but also by additional mechanism(s) followed by metabolism
that is completely different from the cholesteryl esters or apoB100, the other
main components of LDL.