Statin-sensitive endocytosis of albumin by glomerular podocytes

Jeanette Eyre, Kyriakos Ioannou, Blair D. Grubb, Moin A. Saleem, Peter W. Mathieson, Nigel J. Brunskill, Erik I. Christensen, Peter S. Topham

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    66 Citations (Scopus)

    Abstract

    Glomerular podocytes are critical regulators of glomerular permeability via the slit diaphragm and may play a role in cleaning the glomerular filter. Whether podocytes are able to endocytose proteins is uncertain. We studied protein endocytosis in conditionally immortalized mouse and human podocytes using FITC-albumin by direct quantitative assay and by fluorescence microscopy and electron microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human, rat, and mouse podocytes. Both mouse and human podocytes displayed specific one-site binding for FITC-albumin with Kd of 0.91 or 0.44 mg/ml and Bmax of 3.15 or 0.81 μg/mg cell protein, respectively. In addition, they showed avid endocytosis of FITC-albumin with Km of 9.48 or 4.5 mg/ml and Vmax of 474.3 or 97.4 μg·mg cell protein-1·h-1, respectively. Immunoglobulin and transferrin were inefficient competitors of this process, indicating some specificity for albumin. Accumulation of endocytosed albumin could be demonstrated in intracellular vesicles by fluorescence confocal microscopy and electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin. In vivo accumulation of albumin was found in all three species but was most pronounced in the rat. We conclude that podocytes are able to endocytose protein in a statin-sensitive manner. This function is likely to be highly significant in health and disease. In addition, protein endocytosis by podocytes may represent a useful, measurable phenotypic characteristic against which potentially injurious or beneficial interventions can be assessed.

    Original languageEnglish
    Pages (from-to)F674-F681
    Number of pages8
    JournalAmerican Journal of Physiology - Renal Physiology
    Volume292
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2007

    Keywords

    • Nephropathy
    • Permeability
    • Proteinuria
    • Renal
    • Slit diaphragm

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