title: The lipid composition of high-density lipoprotein affects its re-absorption in the kidney by proximal tubule epithelial cells.
abstract: The kidney is believed to play a major role in the clearance of apoA-I (apolipoprotein A-I) and HDL (high-density lipoprotein) particles from the bloodstream. Proximal tubule epithelial cells of the kidney appear to prevent the loss of these proteins in the urine by re-absorbing them from the urinary filtrate. Experiments were undertaken to investigate the factors that regulate the renal re-absorption of apoA-I and small HDL in a transformed human proximal tubule epithelial (HKC-8) cell line. Fluorescent microscopic studies show that HKC-8 cells can readily bind and take up HDL particles. Intracellular localization of fluorescently labelled native HDL shows its accumulation in endocytotic vesicles, in a perinuclear region after 1 h. Binding studies reveal a saturable cell association of (125)I-HDL with the HKC-8 cell surface after 2 h. HKC-8 cells do not degrade apoA-I or other HDL-apoproteins. The specific cell association of lipid-free apoA-I is approx. 2-fold less than that observed for native HDL. Similarly, reconstituted HDL prepared from HDL-apoproteins and pure phospholipids also exhibits a low cell association with the HKC-8 cells. In contrast, reconstituted HDL prepared with the extracted lipids of HDL and pure apoA-I exhibits an even higher cell association than that observed with the native lipoprotein. A detailed characterization of the major lipid classes in reconstituted HDL shows that only cholesteryl ester increases the cell association of the recombinant particles. These results show that the cholesteryl ester content of HDL may play an important role in the re-absorptive salvage of HDL by the proximal tubule cells of the kidney.
authors.affiliation: Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Breznan
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Veereswaran
authors.forename: France J
authors.initials: FJ
authors.lastname: Viau
authors.forename: Tracey A-M
authors.initials: TA
authors.lastname: Neville
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Sparks
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008055:Lipids; D008075:Lipoproteins, HDL