Albumin endocytosis in proximal tubule cells is modulated by angiotensin II through an AT2 receptor-mediated protein kinase B activation

Celso Caruso-Neves, Sang Ho Kwon, William B. Guggino

Research output: Contribution to journalArticle

Abstract

Albumin endocytosis in renal proximal tubule cells is a clathrin- and receptor-mediated mechanism that, in several pathophysiological conditions, is involved in initiating or promoting tubule-interstitial disease. Although much work has been done on this pathway, the regulation of albumin endocytosis in proximal tubule cells is not well understood. Here, we study the modulation by angiotensin II (Ang II) of albumin endocytosis in LLC-PK1, a model of proximal tubule cells. We observed that Ang II increases albumin endocytosis by ≈100% at 10-9 M. This effect is completely reversed by 10-9 M PD123319, a specific AT2 receptor antagonist, but not by losartan, a specific AT1 receptor antagonist, at concentrations up to 10 -7 M. The Ang II effect on albumin endocytosis is also reversed by: phosphoinositide 3-kinase inhibitors LY294002 (2.5 × 10-6 M) or wortmannin (10-7 M), the protein kinase B inhibitor (2 × 10-5 M), and staurosporine (2 × 10-6 M), an inhibitor of 3′-phosphoinositide-dependent kinase 1. Ang II induced the selective phosphorylation of protein kinase B (PKB) at the Thr-308 residue without a change in Ser-473 phosphorylation, a combination that leads to an increase in PKB activity. These effects were completely abolished by 3 × 10-6 M staurosporine or 10-8 M PD123319. Our experiments also showed that PKB is present in the membrane fraction in overnight-starved LLC-PK1 cells. Taken together, these data show that Ang II increases albumin endocytosis through an AT2 receptor mediated by activation of PKB in the plasma membrane, which depends on the basal activity of the phosphatidylinositol 3-kinase.

Original languageEnglish (US)
Pages (from-to)17513-17518
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number48
DOIs
StatePublished - Nov 29 2005

Keywords

  • Kidney
  • Reabsorption
  • Regulation

ASJC Scopus subject areas

  • General

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