Uptake of advanced glycation end products by proximal tubule epithelial cells via macropinocytosis

• Published in: Biochimica et biophysica acta 2013-12, Vol.1833 (12), p.2922-2932
• Main Authors: Gallicchio, Marisa A., Bach, Leon A.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; ADP-Ribosylation Factors - metabolism; Animals; Cell Surface Extensions - drug effects; Cell Surface Extensions - metabolism; Cytoskeletal Proteins - metabolism; Dextrans - metabolism; Diabetes; Down-Regulation - drug effects; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - enzymology; Epithelial Cells - metabolism; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - metabolism; Glycation; Glycation End Products, Advanced - metabolism; Humans; Kidney Tubules, Proximal - cytology; LLC-PK1 Cells; Macropinocytosis; Na+K+ATPase; Nephropathy; p21-Activated Kinases - metabolism; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphotransferases (Alcohol Group Acceptor); Pinocytosis - drug effects; Polymerization - drug effects; rac1 GTP-Binding Protein - metabolism; Rhodamines - metabolism; RNA, Small Interfering - metabolism; Serum Albumin, Bovine - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; Swine; TGF-β; Transforming Growth Factor beta1 - metabolism
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2013.05.024

Chronic hyperglycaemia during diabetes leads to non-enzymatic glycation of proteins to form advanced glycation end products (AGEs) that contribute to nephropathy. We describe AGE uptake in LLC-PK1 and HK2 proximal tubule cell lines by macropinocytosis, a non-specific, endocytic mechanism. AGE–BSA induced dorsal circular actin ruffles and amiloride-sensitive dextran–TRITC uptake, significantly increased AGE–BSA–FITC uptake (167±20% vs BSA control, p