Phosphatidylinositol promotes cholesterol transport and excretion.
Administration of phosphatidylinositol (PI) to New Zealand White rabbits increases HDL negative charge and stimulates reverse cholesterol transport. Intravenously administered PI (10 mg/kg) associated almost exclusively with the HDL fraction in rabbits. PI promoted an increase in the hepatic uptake of plasma free cholesterol (FC) and a 21-fold increase in the biliary secretion of plasma-derived cholesterol. PI also increased cholesterol excretion into the feces by 2.5-fold. PI directly affects cellular cholesterol metabolism. In cholesterol-loaded macrophages, PI stimulated cholesterol mass efflux to lipid-poor reconstituted HDL. PI was about half as effective as cAMP at stimulating efflux, and the effects of cAMP and PI were additive. In cultured HepG2 cells, PI-enriched HDL also enhanced FC uptake from HDL by 3-fold and decreased cellular cholesterol synthesis and esterification. PI enrichment had no effect on the selective uptake of cholesterol esters or on the internalization of HDL particles. PI-dependent metabolic events were efficiently blocked by inhibitors of protein kinase C and the inositol signaling cascade. The data suggest that HDL-PI acts via cell surface ATP binding cassette transporters and signaling pathways to regulate both cellular and intravascular cholesterol homeostasis.
Burgess
Jim W
JW
Liponex, Inc., 1740 Woodroffe Ave, Building 400, Ottawa, Ontario, Canada, K2G 3R8.
Boucher
Jonathan
J
Neville
Tracey A-M
TA
Rouillard
Patricia
P
Stamler
Chris
C
Zachariah
Susha
S
Sparks
Daniel L
DL
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D015398:Signal Transduction; D013997:Time Factors
D004791:Enzyme Inhibitors; D008075:Lipoproteins, HDL; D010716:Phosphatidylinositols; D002784:Cholesterol; D000242:Cyclic AMP; D011493:Protein Kinase C