Effects of advanced glycation end product modification on proximal tubule epithelial cell processing of albumin.
OBJECTIVE
The goal of this work is to understand the cellular effects of advanced glycation end product (AGE)-modified protein on renal proximal tubule cells.


BACKGROUND
A major function of the proximal tubule is to reabsorb and process filtered proteins. Diabetes is characterized by increased quantities of tissue and circulating proteins modified by AGEs. Therefore in diabetes, plasma proteins filtered at the glomerulus and presented to the renal proximal tubule are likely to be highly modified by AGEs.


METHODS
The model system was electrically resistant polarized renal proximal tubular epithelial cells in monolayer culture. The model proteins comprise a well-characterized AGE, methylglyoxal-modified bovine serum albumin (MGO-BSA), and unmodified BSA.


RESULTS
Renal proximal tubular cells handle MGO-BSA and native BSA in markedly disparate ways, including differences in: (1) kinetics of binding, uptake, and intracellular accumulation, (2) processing and fragmentation, and (3) patterns of electrical conductance paralleling temporal changes in binding, uptake and processing.


CONCLUSIONS
These differences support the idea that abnormal protein processing by the renal tubule can be caused by abnormal proteins, thereby forging a conceptual link between the pathogenic role of AGEs and early changes in tubular function that can lead to hypertrophy and nephropathy in diabetes.
Ozdemir
Aylin M
AM
Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Hopfer
Ulrich
U
Rosca
Mariana V
MV
Fan
Xing-Jun
XJ
Monnier
Vincent M
VM
Weiss
Miriam F
MF
D002461:Cell Line, Transformed; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D011765:Pyruvaldehyde / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced; D012710:Serum Albumin, Bovine; D011765:Pyruvaldehyde; D016650:Fluorescein-5-isothiocyanate