| First Author | Dugué-Pujol S | Year | 2007 |
| Journal | J Lipid Res | Volume | 48 |
| Issue | 10 | Pages | 2151-61 |
| PubMed ID | 17652309 | Mgi Jnum | J:126542 |
| Mgi Id | MGI:3761558 | Doi | 10.1194/jlr.M700089-JLR200 |
| Citation | Dugue-Pujol S, et al. (2007) Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration. J Lipid Res 48(10):2151-61 |
| abstractText | 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. |
