An induction in hepatic HDL secretion associated with reduced ATPase expression.
Linoleic acid-phospholipids stimulate high-density lipoprotein (HDL) net secretion from liver cells by blocking the endocytic recycling of apoA-I. Experiments were undertaken to determine whether apoA-I accumulation in the cell media is associated with membrane ATPase expression. Treatment of HepG2 cells with dilinoeoylphosphatidylcholine (DLPC) increased apoA-I secretion fourfold. DLPC also significantly reduced cell surface F1-ATPase expression and reduced cellular ATP binding cassette (ABC)A1 and ABCG1 protein levels by approximately 50%. In addition, treatment of HepG2 cells with the ABC transporter inhibitor, glyburide, stimulated the apoA-I secretory effects of both DLPC and clofibrate. Pretreatment of HepG2 cells with compounds that increased ABC transport protein levels (TO901317, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal, and resveratrol) blocked the DLPC-induced stimulation in apoA-I net secretion. Furthermore, whereas HepG2 cells normally secrete nascent prebeta-HDL, DLPC treatment promoted secretion of alpha-migrating HDL particles. These data show that an linoleic acid-phospholipid induced stimulation in hepatic HDL secretion is related to the expression and function of membrane ATP metabolizing proteins.
Pandey
Nihar R
NR
Lipoprotein and Atherosclerosis Research Group, The University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
Renwick
Joanna
J
Rabaa
Seham
S
Misquith
Ayesha
A
Kouri
Lara
L
Twomey
Erin
E
Sparks
Daniel L
DL
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D003470:Culture Media; D005905:Glyburide / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D019787:Linoleic Acid / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D000071518:Liver X Receptors; D008954:Models, Biological; D057093:Orphan Nuclear Receptors / Q000819:agonists; D010743:Phospholipids / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D003470:Culture Media; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010743:Phospholipids; D034741:RNA, Small Interfering; C116500:acetyl-leucinal-nor-leucinal; D019787:Linoleic Acid; D006180:Proton-Translocating ATPases; D007930:Leucine; D005905:Glyburide