The AGE product N epsilon-(carboxymethyl)lysine serum albumin is a modulator of proteoglycan expression in polarized cultured kidney epithelial cells.
OBJECTIVE
Changes in kidney function in diabetes could be due to changes in the kidney basement membranes. Proteoglycans are important constituents of this kidney extracellular matrix. This study explored the possibility that advanced glycation end products affect proteoglycan synthesis in cultured kidney epithelial cells.


METHODS
Madin Darby Canine Kidney (MDCK) epithelial cells were cultured with either low glucose (5 mmol/l), low glucose with 10 micrograms/ml of N epsilon-(carboxymethyl)lysine bovine serum albumin (CML-BSA) or high glucose (25 mmol/l). From day 7-8 cells were labelled with either [35S]sulphate or [3H]glucosamine for 24 h. Labelled macromolecules were purified by gel and ion exchange chromatography, and isolated proteoglycans analysed by gel chromatography and electrophoresis.


RESULTS
The CML-BSA treatment reduced the proteoglycan synthesis in MDCK cells. Neither the type of glycosaminoglycan chains made nor the molecular size of the chains was affected.


CONCLUSIONS
At concentrations found in the plasma of diabetes patients CML-BSA, decreases proteoglycan expression in kidney epithelial cells. Advanced glycation end products could, accordingly, promote pathological changes in kidneys of diabetics.
Borrebaek
J
J
Institute for Nutrition Research, University of Oslo, Box 1046 Blindern, 0316 Oslo, Norway.
Prydz
K
K
Fjeldstad
K
K
Vuong
T T
TT
Berg
T J
TJ
Holkov
C
C
Kolset
S O
SO
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry*; D011509:Proteoglycans / Q000096:biosynthesis*; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014316:Tritium
D017127:Glycation End Products, Advanced; D011509:Proteoglycans; D012709:Serum Albumin; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; C048496:N(6)-carboxymethyllysine; D005947:Glucose; D008239:Lysine; D005944:Glucosamine