Proximal tubular epithelial cells preferentially endocytose covalently-modified albumin compared to native albumin

Nguyen D.K. Ly, Greg H Tesch, David J. Nikolic-Paterson, Philip Poronnik

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Aim: Albumin can be covalently modified at surface lysine residues and thus the circulation contains a mixture of native albumin (i.e. not modified) and albumin with varying degrees of modification. Uptake and lysosomal degradation of glomerular filtered albumin by proximal tubular cells via the megalin scavenger receptor is considered an important mechanism to limit albumin loss in the urine. However, whether this is a general mechanism of tubular uptake of albumin or if this is restricted to modified albumin is unknown. To address this question, we investigated the uptake of modified versus native albumin by proximal tubular cells. Methods: A well-characterized proximal tubular cell model of albumin uptake was used to compare the uptake of modified albumin (covalent labelling of lysine residues with fluorescent probes) to that of native recombinant human albumin (rHA) labelled with 14C during protein synthesis (14C-rHA). Results: Opossum kidney (OK) cells showed significant uptake of fluorescence-labelled albumin via an endocytosis mechanism. This uptake was inhibited by an equimolar ratio of different types of covalently modified albumin; however, purified bovine serum albumin and rHA failed to compete with the uptake of fluorescence-labelled albumin. In contrast, OK cells failed to endocytose native 14C-rHA despite efficiently endocytosing covalently modified rHA. Conclusion: Our studies show that OK cells preferentially endocytose covalently-modified albumin compared to native albumin. This apparent selectivity of the megalin scavenger receptor complex suggests a specific role for this pathway in the removal of modified albumin from the circulation.

Original languageEnglish
Pages (from-to)121-126
Number of pages6
JournalNephrology
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2019

Keywords

  • advanced glycation end products (AGEs)
  • albuminuria
  • tubular cells

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