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Megalin mediates the uptake of angiotensin II in proximal tubule cells
Author(s) -
GonzalezVillalobos Romer Andres,
Satou Ryousuke,
Katsurada Akemi,
Kobori Hiroyuki,
Hammond Timothy Grant,
Navar L. G.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1245-c
Subject(s) - angiotensin ii , endocytosis , chemistry , flow cytometry , olmesartan , receptor , candesartan , tubule , cell , proximal tubule , medicine , microbiology and biotechnology , kidney , endocrinology , biochemistry , biology , blood pressure
Background: Megalin and the Ang II type I receptor (AT 1 R) are coexpressed in the renal proximal tubule where megalin is involved in endocytosis and degradation of proteins that escape the glomerular barrier. Because Ang II uptake by AT 1 R‐expressing BN/MSV cells (a non‐renal cell line) is partially mediated by megalin, we tested if megalin mediates Ang II uptake in proximal tubule cells. Methods: Cultured proximal tubule cells (NRK‐52E cells) were exposed to fluorescent Ang II for 4 hours (Alexa488‐Ang II, 100 nM). Olmesartan (or Candesartan 10 μM) and anti‐megalin antisera (or albumin 1 mg/mL) were used to block the AT 1 R and the megalin pathways respectively. Flow cytometry was used to measure single cell‐associated fluorescence. Confocal or fluorescence microscope systems were used for image capturing and analysis. Results: In flow cytometry experiments, both anti‐megalin antisera and AT 1 R blockers significantly reduced Ang II uptake (30% and 60% reductions respectively, p <0.05 vs. positive control). In imaging experiments, Ang II accumulated mostly in a perinuclear area and this accumulation was reduced by treatment with albumin, AT 1 R blockers or both. Conclusion: Megalin mediates Ang II uptake into proximal tubule cells in addition to the AT 1 R. Because megalin is responsible for the scavenging of proteins in the tubular fluid, megalin‐mediated Ang II uptake might help to regulate intrarenal Ang II levels.