title: Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration.
abstract: We investigated in vivo catabolism of apolipoprotein A-II (apo A-II), a major determinant of plasma HDL levels. Like apoA-I, murine apoA-II (mapoA-II) and human apoA-II (hapoA-II) were reabsorbed in the first segment of kidney proximal tubules of control and hapoA-II-transgenic mice, respectively. ApoA-II colocalized in brush border membranes with cubilin and megalin (the apoA-I receptor and coreceptor, respectively), with mapoA-I in intracellular vesicles of tubular epithelial cells, and was targeted to lysosomes, suggestive of degradation. By use of three transgenic lines with plasma hapoA-II concentrations ranging from normal to three times higher, we established an association between plasma concentration and renal catabolism of hapoA-II. HapoA-II was rapidly internalized in yolk sac epithelial cells expressing high levels of cubilin and megalin, colocalized with cubilin and megalin on the cell surface, and effectively competed with apoA-I for uptake, which was inhibitable by anti-cubilin antibodies. Kidney cortical cells that only express megalin internalized LDL but not apoA-II, apoA-I, or HDL, suggesting that megalin is not an apoA-II receptor. We show that apoA-II is efficiently reabsorbed in kidney proximal tubules in relation to its plasma concentration.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U872, Equipe 6, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dugué-Pujol
authors.forename: Xavier
authors.initials: X
authors.lastname: Rousset
authors.forename: Danielle
authors.initials: D
authors.lastname: Château
authors.forename: Danièle
authors.initials: D
authors.lastname: Pastier
authors.forename: Christophe
authors.initials: C
authors.lastname: Klein
authors.forename: Jeannine
authors.initials: J
authors.lastname: Demeurie
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cywiner-Golenzer
authors.forename: Michèle
authors.initials: M
authors.lastname: Chabert
authors.forename: Pierre
authors.initials: P
authors.lastname: Verroust
authors.forename: Jean
authors.initials: J
authors.lastname: Chambaz
authors.forename: François-Patrick
authors.initials: FP
authors.lastname: Châtelet
authors.forename: Athina-Despina
authors.initials: AD
authors.lastname: Kalopissis
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000097:blood* / Q000378:metabolism*; D001053:Apolipoproteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008297:Male; D008660:Metabolism; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism
chemical_list: D016633:Apolipoprotein A-II; D001053:Apolipoproteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor