Apolipoprotein A-II is catabolized in the kidney as a function of its plasma concentration
| Autor: | Xavier Rousset, A.-D. Kalopissis, Danièle Pastier, Jeannine Demeurie, Jean Chambaz, Charlotte Cywiner-Golenzer, Christophe Klein, Danielle Château, Sonia Dugué-Pujol, François-Patrick Châtelet, Michèle Chabert, Pierre J. Verroust |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Brush border Apolipoprotein B Apolipoprotein A-II yolk sac cells Mice Transgenic Receptors Cell Surface QD415-436 Kidney urologic and male genital diseases Biochemistry Mice Endocrinology proximal tubule Internal medicine cubilin polycyclic compounds medicine Animals Humans Receptor Yolk Sac biology Chemistry Catabolism Cell Membrane nutritional and metabolic diseases Kidney metabolism Epithelial Cells Cell Biology Cubilin Rats Cell biology Low Density Lipoprotein Receptor-Related Protein-2 Apolipoproteins Kidney Tubules Metabolism medicine.anatomical_structure mouse kidney cortical cells high density lipoprotein biology.protein Female lipids (amino acids peptides and proteins) megalin |
| Zdroj: | Journal of Lipid Research, Vol 48, Iss 10, Pp 2151-2161 (2007) |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.m700089-jlr200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|