Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration.

We investigated in vivo catabolism of apolipopro- tein 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 lyso- somes, suggestive of degradation. By use of three transgenic lines with plasma hapoA-II concentrations ranging from nor- mal to three times higher, we established an association be- tween 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 ex- press 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.— Dugue ´-Pujol, S., X. Rousset, D. Chateau, D. Pastier, C. Klein, J. Demeurie, C. Cywiner-Golenzer, M. Chabert, P. Verroust, J. Chambaz, F-P. Chatelet, and A-D. Kalopissis. Apolipopro- tein A-II is catabolized in the kidney as a function of its plasma concentration. J. Lipid Res. 2007. 48: 2151-2161.