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Modulation of Proximal Tubule Cell Endocytic Capacity by Nephrotic Levels of Albumin
Author(s) -
Long Kimberly R,
Rbaibi Youssef,
Weisz Ora A
Publication year - 2019
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.2019.33.1_supplement.751.4
Subject(s) - albumin , endocytic cycle , bovine serum albumin , serum albumin , chemistry , endocrinology , medicine , oxidative stress , kidney , nephrotic syndrome , endocytosis , biochemistry , cell , biology
The glomerulus and proximal tubule (PT) of the kidney coordinate to prevent the excretion of albumin and other plasma proteins in the urine. Disruption of the glomerular filtration barrier in nephrotic disease overwhelms the endocytic capacity of the PT, leading to proteinuria. Nephrotic levels of albumin are cytotoxic to the PT and trigger cell signaling and adaptive responses. Recent studies have suggested that fatty acids carried by albumin cause mitochondrial oxidative damage that contribute to PT toxicity. However, fundamental questions about the PT response to albumin remain unanswered. Discordant results using different PT cell models, treatment conditions, and outcome measures have further complicated our understanding of how PT cells respond to albumin and its metabolic load in different disease conditions. We used a recently developed cell culture model that recapitulates key in vivo features of PT function to examine how PT cells adapt their endocytic capacity in response to nephrotic levels of albumin. We treated opossum kidney cells cultured under orbital shear stress with physiologic or nephrotic levels of apically‐added Fraction V bovine serum albumin (BSA), fatty acid‐free or palmitate‐loaded BSA, or human serum and monitored the cells for oxidative damage, megalin expression levels, and endocytic capacity. None of these parameters were altered by incubation with fatty acid‐free BSA, however, incubation with 20 mg/mL Fraction V BSA resulted in a rapid and reproducible decrease in endocytic capacity (within 3 h) followed by increased oxidative stress and decreased megalin expression measured after overnight treatment. Palmitate‐loaded BSA and human serum elicited very different profiles of cellular changes (relative to Fraction V BSA and each other) over a 3 – 48 h incubation period. These data suggest that PT cells initiate different adaptive signals in response to the composition of the metabolic load on endocytosed albumin. Our results have implications for the development of therapeutic strategies to mitigate disease‐dependent proteinuric tubular injury. Support or Funding Information NIH R01‐DK101484; NIH R01‐DK100357; NIH P30‐DK079307 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .